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Frontiers in Oncology 2023Mediastinal tumors, particularly non-neuroendocrine thymic epithelial tumors (TET) are relatively uncommon, posing challenges for extensive epidemiological studies. This...
INTRODUCTION
Mediastinal tumors, particularly non-neuroendocrine thymic epithelial tumors (TET) are relatively uncommon, posing challenges for extensive epidemiological studies. This study presents a comprehensive analysis of these tumors in the United States (US) and Germany (GER) from 1999 to 2019.
METHODS
Patients aged 0-19 (n=478) and ≥20 years (n=17,459) diagnosed with malignant tumors of the anterior mediastinum were identified from the Surveillance, Epidemiology, and End Results registry (SEER) and the Zentrum für Krebsregisterdaten (ZfKD) databases.
RESULTS
Among patients aged ≥20 years, TETs accounted for the most prevalent anterior mediastinal tumors (US/GER: 63%/64%), followed by lymphomas (14%/8%). For patients <20 years, predominant tumors included germ cell tumors (42%/14%), lymphomas (38%/53%), and TETs (10%/27%). The overall annual incidence of thymoma was 2.2/2.64 (US/GER) per million inhabitants and for thymic carcinomas 0.48/0.42. The male-to-female ratio was 1:1.09/1.03, and the mean age 59.48 ± 14.89/61.33 ± 13.94. Individuals with thymomas, but not thymic carcinomas, exhibited a 21%/29% significantly heightened risk of developing secondary malignancies compared to controls with non-thymic primary tumors.
DISCUSSION
This study provides a comparative analysis of anterior mediastinal tumors, particularly TETs, in the US and GER over the past two decades. Furthermore, it highlights a significantly elevated incidence of secondary malignancies in thymoma patients.
PubMed: 38264756
DOI: 10.3389/fonc.2023.1308989 -
World Journal of Surgical Oncology Jan 2024To explore the risk factors for disease progression after initial treatment of type B thymomas using a predictive nomogram model.
OBJECTIVE
To explore the risk factors for disease progression after initial treatment of type B thymomas using a predictive nomogram model.
METHODS
A single-center retrospective study of patients with type B thymoma was performed. The Cox proportional hazard model was used for univariate and multivariate analyses. Variables with statistical and clinical significance in the multivariate Cox regression were integrated into a nomogram to establish a predictive model for disease progression.
RESULTS
A total of 353 cases with type B thymoma were retrieved between January 2012 and December 2021. The median follow-up was 58 months (range: 1-128 months). The 10-year progression-free survival (PFS) was 91.8%. The final nomogram model included R0 resection status and Masaoka stage, with a concordance index of 0.880. Non-R0 resection and advanced Masaoka stage were negative prognostic factors for disease progression (p < 0.001). No benefits of postoperative radiotherapy (PORT) were observed in patients with advanced stage and non-R0 resection (p = 0.114 and 0.284, respectively).
CONCLUSION
The best treatment strategy for type B thymoma is the detection and achievement of R0 resection as early as possible. Long-term follow-up is necessary, especially for patients with advanced Masaoka stage and who have not achieved R0 resection. No prognostic benefits were observed for PORT.
Topics: Humans; Nomograms; Thymoma; Retrospective Studies; Prognosis; Disease Progression; Thymus Neoplasms
PubMed: 38263144
DOI: 10.1186/s12957-023-03293-2 -
Cancers Jan 2024Lung cancer screening with low-dose helical computed tomography (LDCT) reduces mortality in high-risk subjects. Cigarette smoking is linked to up to 90% of lung cancer...
BACKGROUND
Lung cancer screening with low-dose helical computed tomography (LDCT) reduces mortality in high-risk subjects. Cigarette smoking is linked to up to 90% of lung cancer deaths. Even more so, it is a key risk factor for many other cancers and cardiovascular and pulmonary diseases. The Smokers health Multiple ACtions (SMAC-1) trial aimed to demonstrate the feasibility and effectiveness of an integrated program based on the early detection of smoking-related thoraco-cardiovascular diseases in high-risk subjects, combined with primary prevention. A new multi-component screening design was utilized to strengthen the framework on conventional lung cancer screening programs. We report here the study design and the results from our baseline round, focusing on oncological findings.
METHODS
High-risk subjects were defined as being >55 years of age and active smokers or formers who had quit within 15 years (>30 pack/y). A PLCO threshold >2% was chosen. Subject outreach was streamlined through media campaign and general practitioners' engagement. Eligible subjects, upon written informed consent, underwent a psychology consultation, blood sample collection, self-evaluation questionnaire, spirometry, and LDCT scan. Blood samples were analyzed for pentraxin-3 protein levels, interleukins, microRNA, and circulating tumor cells. Cardiovascular risk assessment and coronary artery calcium (CAC) scoring were performed. Direct and indirect costs were analyzed focusing on the incremental cost-effectiveness ratio per quality-adjusted life years gained in different scenarios. Personalized screening time-intervals were determined using the "Maisonneuve risk re-calculation model", and a threshold <0.6% was chosen for the biennial round.
RESULTS
In total, 3228 subjects were willing to be enrolled. Out of 1654 eligible subjects, 1112 participated. The mean age was 64 years (M/F 62/38%), with a mean PLCO of 5.6%. Former and active smokers represented 23% and 77% of the subjects, respectively. At least one nodule was identified in 348 subjects. LDCTs showed no clinically significant findings in 762 subjects (69%); thus, they were referred for annual/biennial LDCTs based on the Maisonneuve risk (mean value = 0.44%). Lung nodule active surveillance was indicated for 122 subjects (11%). Forty-four subjects with baseline suspicious nodules underwent a PET-FDG and twenty-seven a CT-guided lung biopsy. Finally, a total of 32 cancers were diagnosed, of which 30 were lung cancers (2.7%) and 2 were extrapulmonary cancers (malignant pleural mesothelioma and thymoma). Finally, 25 subjects underwent lung surgery (2.25%). Importantly, there were zero false positives and two false negatives with CT-guided biopsy, of which the patients were operated on with no stage shift. The final pathology included lung adenocarcinomas (69%), squamous cell carcinomas (10%), and others (21%). Pathological staging showed 14 stage I (47%) and 16 stage II-IV (53%) cancers.
CONCLUSIONS
LDCTs continue to confirm their efficacy in safely detecting early-stage lung cancer in high-risk subjects, with a negligible risk of false-positive results. Re-calculating the risk of developing lung cancer after baseline LDCTs with the Maisonneuve model allows us to optimize time intervals to subsequent screening. The Smokers health Multiple ACtions (SMAC-1) trial offers solid support for policy assessments by policymakers. We trust that this will help in developing guidelines for the large-scale implementation of lung cancer screening, paving the way for better outcomes for lung cancer patients.
PubMed: 38254906
DOI: 10.3390/cancers16020417 -
Cancers Jan 2024Thymic epithelial tumors (TETs), which include thymomas and thymic carcinomas, are a rare, heterogeneous group of malignancies that originate from the thymus gland. As... (Review)
Review
Thymic epithelial tumors (TETs), which include thymomas and thymic carcinomas, are a rare, heterogeneous group of malignancies that originate from the thymus gland. As an important organ of immune cell development, thymic tumors, particularly thymomas, are often associated with paraneoplastic autoimmune disorders. The advances in targeted therapies for both solid and hematologic malignancies have resulted in improved patient outcomes, including better and more durable efficacy and improved toxicity. Targeted therapies have also been investigated in the treatment of TETs, though the results have largely been modest. These have included somatostatin-receptor-targeting therapies, KIT- and EGFR-directed tyrosine kinase inhibitors, epigenetic modulators, anti-angiogenesis agents, and agents targeting the cell proliferation and survival pathways and cell cycle regulators. Numerous investigated treatments have failed or underperformed due to a lack of a strong biomarker of efficacy. Ongoing trials are attempting to expand on previous experiences, including the exploration of effective drugs in early-stage disease. Novel combination therapy strategies are also undergoing evaluation, with the goal of augmenting efficacy and understanding the toxicity while expanding the biomarkers of efficacy and safety. With advances in technology to improve target identification and drug delivery, old targets may become new opportunities, and the subsequently developed drugs may find their place in the treatment of thymic tumors.
PubMed: 38254905
DOI: 10.3390/cancers16020416 -
Aberrant DNA Methylation of NPTX2 as an Indicator of Malignant Behavior in Thymic Epithelial Tumors.Cancers Jan 2024Thymic epithelial tumors (TET) consist of thymomas, thymic carcinoma (TC), and neuroendocrine tumors of the thymus (NECTT). Genetic and epigenetic alterations in TET...
Thymic epithelial tumors (TET) consist of thymomas, thymic carcinoma (TC), and neuroendocrine tumors of the thymus (NECTT). Genetic and epigenetic alterations in TET have been the focus of recent research. In the present study, genome-wide screening was performed on aberrantly methylated CpG islands in TET, and this identified neuronal pentraxin 2 (NTPX2) as a significantly hypermethylated CpG island in TC relative to thymomas. NPTX2 is released from pre-synaptic cells in response to neuronal activity/seizure, and plays a role in host immunity and acute inflammation. TET samples were obtained from 38 thymomas, 25 TC, and 6 NECTT. The DNA methylation, mRNA, and protein expression levels of were examined. The DNA methylation rate of the gene was significantly higher in TC than in the normal thymus and thymomas, except B3. The mRNA expression level of was lower in TC than in the normal thymus. An inverse relationship was observed between mRNA expression levels and methylation levels. Relapse-free survival was shorter in patients with high DNA methylation levels than in those with low DNA methylation levels. NECTT showed very high mRNA and protein expression levels and low DNA methylation levels of NPTX2. NPTX2 may function as a tumor suppressor in TC, and have an oncogenic function in NECTT.
PubMed: 38254821
DOI: 10.3390/cancers16020329 -
Predicting disability and mortality in CV2/CRMP5-IgG associated paraneoplastic neurologic disorders.Annals of Clinical and Translational... Mar 2024We aimed to investigate the prognostic factors associated with clinical outcomes in CV2/Collapsin response-mediator protein 5 (CRMP5)-IgG paraneoplastic neurologic...
BACKGROUND
We aimed to investigate the prognostic factors associated with clinical outcomes in CV2/Collapsin response-mediator protein 5 (CRMP5)-IgG paraneoplastic neurologic disorders (PND).
METHODS
This is a retrospective study of patients with CV2/CRMP5-IgG PND evaluated between 2002-2022. We examined the association of clinical variables (including age, clinical phenotype [autoimmune encephalopathy, myelopathy, polyneuropathy/radiculopathy, MG, cerebellar ataxia, chorea, optic neuropathy], cancer) with three clinical outcomes (wheelchair dependence, modified Rankin Scale [mRS], mortality) using univariate logistic regression and Cox proportional hazards modeling. Kaplan-Meier estimates were used to determine the probability of survival.
RESULTS
Twenty-seven patients (56% female) with CV2/CRMP5-IgG PND were identified with a median follow-up of 54 months (IQR = 11-102). An underlying tumor was identified in 15 patients (56%) including small cell lung cancer (SCLC) (8, [53%]), thymoma (4, [27%]), and other histologies (3, [20%]). At last follow-up, 10 patients (37%) needed a wheelchair for mobility and this outcome was associated with myelopathy (HR = 7.57, 95% CI = 1.87-30.64, P = 0.005). Moderate-severe mRS = 3-5 was associated with CNS involvement (encephalopathy, myelopathy, or cerebellar ataxia) (OR = 7.00, 95% CI = 1.18-41.36, P = 0.032). The probability of survival 4 years after symptom onset was 66%. Among cancer subtypes, SCLC (HR = 18.18, 95% CI = 3.55-93.04, P < 0.001) was significantly associated with mortality, while thymoma was not.
INTERPRETATION
In this retrospective longitudinal study of CV2/CRMP5-IgG PND, patients with CNS involvement, particularly myelopathy, had higher probability of disability. SCLC was the main determinant of survival in this population.
Topics: Humans; Female; Male; Retrospective Studies; Nerve Tissue Proteins; Microtubule-Associated Proteins; Cerebellar Ataxia; Longitudinal Studies; Autoantibodies; Small Cell Lung Carcinoma; Nervous System Diseases; Thymoma; Thymus Neoplasms; Lung Neoplasms; Immunoglobulin G; Spinal Cord Diseases
PubMed: 38251800
DOI: 10.1002/acn3.51991 -
Medicine Jan 2024Acute respiratory distress syndrome (ARDS) is an acute respiratory illness characterized by bilateral chest radiographic opacities and severe hypoxemia due to...
INTRODUCTION
Acute respiratory distress syndrome (ARDS) is an acute respiratory illness characterized by bilateral chest radiographic opacities and severe hypoxemia due to noncardiogenic pulmonary edema. However, ARDS due to sing lung injury is rare. In this article, we describe a case of a female patient who developed ARDS during surgery and 1-lung mechanical ventilation.
METHODS
A 53-year-old woman developed hypoxemia 2 days after undergoing thymoma excision. Antibiotics, diuretics, expectorants, and supportive treatment strategies (noninvasive positive-pressure breathing, high-flow nasal oxygen) were used for approximately 3 days after admission to the intensive care unit (ICU), but the patient's oxygen index continued to deteriorate. Considering the possibility of ARDS being induced by 1-lung mechanical ventilation, prone positioning, methylprednisolone, nintedanib, and acetylcysteine were administered.
RESULT
Oxygenation improves greatly after 23 days admitted to ICU. Chest computed tomography shows a real reversal of the disease. The patient was discharged from ICU 29 days after admission to the ICU and was discharged from the hospital after 36 days admitted to ICU.
CONCLUSION
In this report, we describe a rare case of ARDS involved 1 lung, in which we successfully used noninvasive positive-pressure breathing, high-flow nasal oxygen, and prone positioning to succeed improvement of clinical outcomes. The use of the prone position has benefits in nonintubated patient with ARDS even involved 1 lung.
Topics: Humans; Female; Middle Aged; Respiration, Artificial; Thymoma; Lung; Respiratory Distress Syndrome; Hypoxia; Thymus Neoplasms; Oxygen; Prone Position
PubMed: 38241580
DOI: 10.1097/MD.0000000000035373 -
Medicine Jan 2024Pure white cell aplasia (PWCA) is a rare paraneoplastic syndrome that occurs in patients with thymomas. Currently, the pathogenesis and treatment of this disease remain... (Review)
Review
RATIONALE
Pure white cell aplasia (PWCA) is a rare paraneoplastic syndrome that occurs in patients with thymomas. Currently, the pathogenesis and treatment of this disease remain in the exploratory stage.
PATIENT CONCERNS
We report a 68-year-old woman with thymoma experienced PWCA involvement as her first presentation. The patient had high fever and agranulocytosis at the onset of the disease. The white blood cell count in the complete blood count was 1.9 × 109/L with a neutrophil of 0.1 × 109/L. The bone marrow aspirates showed decreased granulocyte proliferation. Computed tomography showed a large mass in the anterior mediastinum.
DIAGNOSES
The final diagnosis of our patient was PWCA and thymoma.
INTERVENTIONS
She underwent a thymectomy and cyclosporine A administration during first remission.
OUTCOMES
Long-term remission was achieved following the readministration of cyclosporine A after the disease recurrence.
LESSONS
PWCA or agranulocytosis with thymoma has been confirmed to be an extremely rare disease. Thymomas with PWCA correlate with autoimmunity. From this case study and the literature review, we concluded that the pathogenesis of thymomas in PWCA is mainly related to the activation of autoreactive T cells. Thymectomy and the immunosuppressive drug, cyclosporine A, were chosen for treatment. The patient's granulocyte levels were unable to recover after surgery because of the inability to promptly clear activated T cells. After surgery, cyclosporine A continued to take for a long time. Thymectomy combined with prolonged cyclosporine A administration may be an effective method for treating this rare disease.
Topics: Humans; Female; Aged; Thymoma; Cyclosporine; Thymectomy; Rare Diseases; Neoplasm Recurrence, Local; Thymus Neoplasms; Agranulocytosis
PubMed: 38241556
DOI: 10.1097/MD.0000000000036920 -
Frontiers in Immunology 2023Tubulin epsilon and delta complex 2 (TEDC2) is widely expressed in various human tissues and primarily governs centriole stability. However, the biological significance...
INTRODUCTION
Tubulin epsilon and delta complex 2 (TEDC2) is widely expressed in various human tissues and primarily governs centriole stability. However, the biological significance of TEDC2 in pan-cancer is unclear.
METHODS
In this study, we employed R software and various online bioinformatics analysis tools to investigate the functional attributes of TEDC2 in human tumours and its potential involvement in immune response. The status of TEDC2 expression was evaluated in samples from the TCGA and GEO datasets, as well as in tumour and corresponding normal samples from the TCGA database. Subsequently, Kaplan-Meier estimates, clinical correlations, and univariate Cox regressions were used to analyze the 33 types of tumors from TCGA and determine the prognostic significance of TEDC2. Moreover, nomogram models were formulated using three distinct tumours, namely kidney renal clear cell carcinoma (KIRC), lung adenocarcinoma (LUAD), and liver hepatocellular carcinoma (LIHC), to evaluate the prognostic significance of TEDC2 in tumours. Furthermore, TEDC2 was investigated for its correlation with the levels of immune cell infiltration, and a functional enrichment analysis was conducted to identify potential signalling pathways involving TEDC2.
RESULTS
Differential analysis revealed that 16 tumour types expressed TEDC2 to a greater extent than normal tissues. The abnormal expression of TEDC2 can predict survival outcomes in patients with adrenocortical carcinoma (ACC), KIRC, kidney renal papillary cell carcinoma (KIRP), LUAD, LIHC, lower grade glioma (LGG), and thymoma (THYM). Subsequent results indicated that TEDC2 has the ability to influence ECM regulators, cell cycle, and Immune checkpoint-associated signalling pathways, which could potentially lead to a poor prognosis and tumour progression.
DISCUSSION
TEDC2 has been identified as a potential therapeutic target that could predict the prognosis of multiple tumour types, making it a promising target for reversing tumour development.
Topics: Humans; Tubulin; Prognosis; Carcinoma, Hepatocellular; Carcinoma, Renal Cell; Adenocarcinoma of Lung; Thymus Neoplasms; Liver Neoplasms; Kidney Neoplasms; Lung Neoplasms; Adrenal Cortex Neoplasms
PubMed: 38239349
DOI: 10.3389/fimmu.2023.1272108 -
BMC Cancer Jan 2024The efficacy and safety of subxiphoid thoracoscopic thymectomy (SVATS) for early thymoma are unknown. The purposes of this meta-analysis were to evaluate the... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
The efficacy and safety of subxiphoid thoracoscopic thymectomy (SVATS) for early thymoma are unknown. The purposes of this meta-analysis were to evaluate the effectiveness and safety of SVATS for early thymoma, to compare it with unilateral intercostal approach video thoracoscopic surgery (IVATS) thymectomy, and to investigate the clinical efficacy of modified subxiphoid thoracoscopic thymectomy (MSVATS) for early anterior mediastinal thymoma.
METHODS
Original articles describing subxiphoid and unilateral intercostal approaches for thoracoscopic thymectomy to treat early thymoma published up to March 2023 were searched from PubMed, Embase, and the Cochrane Library. Standardized mean differences (SMDs) and 95% confidence intervals (CIs) were calculated and analyzed for heterogeneity. Clinical data were retrospectively collected from all Masaoka stage I and II thymoma patients who underwent modified subxiphoid and unilateral intercostal approach thoracoscopic thymectomies between September 2020 and March 2023. The operative time, intraoperative bleeding, postoperative drainage, extubation time, postoperative hospital stay, postoperative visual analog pain score (VAS), and postoperative complications were compared, and the clinical advantages of the modified subxiphoid approach for early-stage anterior mediastinal thymoma were analyzed.
RESULTS
A total of 1607 cases were included in the seven studies in this paper. Of these, 591 cases underwent SVATS thymectomies, and 1016 cases underwent IVATS thymectomies. SVATS thymectomy was compared with IVATS thymectomy in terms of age (SMD = - 0.09, 95% CI: -0.20 to - 0.03, I = 20%, p = 0.13), body mass index (BMI; SMD = - 0.10, 95% CI: -0.21 to - 0.01, I = 0%, p = 0.08), thymoma size (SMD = - 0.01, 95% CI: -0.01, I = 0%, p = 0.08), operative time (SMD = - 0.70, 95% CI: -1.43-0.03, I = 97%, p = 0.06), intraoperative bleeding (SMD = - 0.30. 95% CI: -0.66-0.06, I = 89%, p = 0.10), time to extubation (SMD = - 0.34, 95%CI: -0.73-0.05, I = 91%, p = 0.09), postoperative hospital stay (SMD = - 0.40, 95% CI: -0.93-0.12, I = 93%, p = 0.13), and postoperative complications (odds ratio [OR] = 0.94, 95% CI: 0.42-2.12, I = 57%, p = 0.88), which were not statistically significantly different between the SVATS and IVATS groups. However, the postoperative drainage in the SVATS group was less than that in the IVATS group (SMD = - 0.43, 95%CI: -0.84 to - 0.02, I = 88%, p = 0.04), and the difference was statistically significant. More importantly, the postoperative VAS was lower in the SVATS group on days 1 (SMD = - 1.73, 95%CI: -2.27 to - 1.19, I = 93%, p < 0.00001), 3 (SMD = - 1.88, 95%CI: -2.84 to - 0.81, I = 97%, p = 0.0005), and 7 (SMD = - 1.18, 95%CI: -2.28 to - 0.08, I = 97%, p = 0.04) than in the IVATS group, and these differences were statistically significant. A total of 117 patients undergoing thoracoscopic thymectomy for early thymoma in the Department of Thoracic Surgery of the Second Hospital of Jilin University were retrospectively collected and included in the analysis, for which a modified subxiphoid approach was used in 42 cases and a unilateral intercostal approach was used in 75 cases. The differences between the two groups (MSVATS vs. IVATS) in general clinical characteristics such as age, sex, tumor diameter, Masaoka stage, Word Health Organization (WHO) stage, and intraoperative and postoperative conditions, including operative time, postoperative drainage, extubation time, postoperative hospital stay, and postoperative complication rates, were not statistically significant (p > 0.05), while BMI, intraoperative bleeding, and VAS on postoperative days 1, 3, and 7 were all statistically significant (p < 0.05) in the MSVATS group compared with the IVATS group.
CONCLUSION
The meta-analysis showed that the conventional subxiphoid approach was superior in terms of postoperative drainage and postoperative VAS pain scores compared with the unilateral intercostal approach. Moreover, the modified subxiphoid approach had significant advantages in intraoperative bleeding and postoperative VAS pain scores compared with the unilateral intercostal approach. These results indicate that MSVATS can provide more convenient operation conditions, a better pleural cavity view, and a more complete thymectomy in the treatment of early thymoma, indicating that is a safe and feasible minimally invasive surgical method.
Topics: Humans; Thymoma; Retrospective Studies; Thoracic Surgery, Video-Assisted; Thymus Neoplasms; Postoperative Complications; Pain, Postoperative
PubMed: 38233754
DOI: 10.1186/s12885-024-11832-7