Prognosis of unresected versus resected early-stage pulmonary carcinoid tumors ≤3 cm in size: A population-based study.

PURPOSE: The observation-based prognosis, rather than resection, for small carcinoid tumors is still unclear. This lack of clarity has important implications for counseling elderly patients or patients for whom surgical resection poses a high risk. This study compared the outcomes of observation and surgical resection in patients with pulmonary carcinoid (PC) tumors ≤3 cm in size without metastasis. METHODS: Data of patients with PC tumors with ≤3 cm in diameter and without lymph node and distant metastases were retrieved from Surveillance, Epidemiology, and End Results (SEER) registry. To reduce the inherent bias of retrospective studies, propensity score matching analysis was performed. Overall survival (OS) and lung carcinoid-specific survival (LCSS) were analyzed using Kaplan-Meier plots. Multivariate analysis was used to determine predictors of LCSS in different size subgroups. RESULTS: In total, 4552 patients with early-stage PCs ≤3 cm in diameter, including 435 (9.56%) who were observed and 4117 (90.44%) treated by surgery, were recruited. Patients with surgery had significantly better OS and LCSS than those who were observed. However, patients with observation had comparable LCSS to those with surgery for PCs with tumor diameters ≤1 cm. Multivariate analysis indicated that surgical resection was an independent prognostic factor for LCSS in 1 cm < tumors ≤2 cm, and 2 cm < tumors ≤3 cm groups, but not for tumors ≤1 cm in diameter. CONCLUSION: Surgical resection of small PCs is associated with a survival advantage over observation. However, for early PCs ≤1 cm in diameter, observation may be considered in patients with high risk for surgical resection.

Ten-Year Follow-Up of Lung Cancer Patients with Resected Stage IA Invasive Non-Small Cell Lung Cancer.

OBJECTIVE: The purpose of this study was to assess 10-year follow-up outcomes after surgical resection in patients with stage IA invasive non-small cell lung cancer (NSCLC) based on postoperative pathological diagnosis. METHODS: Patients with stage IA invasive NSCLC who underwent resection between December 2008 and December 2013 were reviewed. Patients were categorized into the pure-ground glass opacity (pGGO), mixed-ground glass opacity (mGGO), and solid groups based on consolidation to tumor ratio (CTR). Postoperative survival and risk of recurrence and developing secondary primary lung cancer were analyzed in each group. RESULTS: Among the 645 stage IA invasive NSCLC, the 10-year overall survival and recurrence-free survival rate was 79.38% and 77.44%, respectively. The 10-year overall survival for pGGO, mGGO, and solid group of patients was 95.08%, 86.21%, and 72.39%, respectively. The respective recurrence-free survival rate was 100%, 89.82%, and 65.83%. Multivariable Cox regression analysis associated tumor size and GGO components with recurrence and younger age, and tumors with GGO components were associated with longer overall survival. The cumulative incidence curve indicated no recurrence of GGO lung cancer ≥ 5 years postoperatively. Our cohort indicated that the number and stations of dissected lymph node did not influence long-term prognosis of IA invasive NSCLC. CONCLUSIONS: Recurrence of invasive stage IA NSCLC with GGO was more prevalent in patients with tumor size >1 cm and CTR > 0.5, occurring within 5 years after surgery. This will provide important evidence for follow-up strategies in these patients.

Prognostic value of KRAS G12V mutation in lung adenocarcinoma stratified by stages and radiological features.

OBJECTIVE: KRAS G12V is one of the most common KRAS mutation variants in lung adenocarcinoma (LUAD), and yet its prognostic value is still unrevealed. In this study, we investigated the clinicopathologic characteristics and prognostic value of the KRAS G12V mutation in LUAD. METHODS: Data of 3829 patients who underwent LUAD resection between 2008 and 2020 were collected. Mutations were classified as wild-type, G12V, or non-G12V. The clinicopathologic characteristics, postoperative outcomes, and recurrence pattern were analyzed among groups. RESULTS: In total, 3554 patients were wild-type and 275 patients harbored a KRAS mutation: 60 patients with G12V (22.2%) and 215 patients with non-G12V (77.8%). The KRAS G12V mutation was more frequent in male patients, older patients (≥60 years), former/current smokers, those patients with radiologic solid nodules, and those with highly invasive histologic subtypes. Tumors carrying KRAS G12V mutation exhibited elevated programmed death-ligand 1 expression in comparison with wild-type tumors. KRAS G12V was more prevalent in older patients and had less lymphovascular invasion compared with other mutation types. FGF3, RET, and KDR co-mutations occurred more frequently in the KRAS G12V group. Multivariate analysis demonstrated that the KRAS G12V mutation was an independent prognostic factor in stage Ⅰ tumors, whereas the KRAS non-G12V mutation was not. KRAS G12V was associated with early recurrence and locoregional recurrence. CONCLUSIONS: The KRAS G12V mutation was associated with aggressive clinical-pathologic phenotype and early recurrence. To note, this mutation exhibited a significantly worse prognosis in patients with part-solid and stage Ⅰ lung adenocarcinoma. Meanwhile, the prognostic significance of KRAS G12C and G12V variants was comparable.

Effect of organic acids on the solid-state polymorphic phase transformation of piracetam.

Metastable polymorphs are frequently used in oral solid dosage forms to enhance the absorption of poorly water-soluble drug compounds. However, the solid phase transformation from the metastable polymorph to the thermodynamically stable polymorph during manufacturing or storage poses a major challenge for product development and quality control. Here, we report that low-content organic acids can exhibit distinct effects on the solid-state polymorphic phase transformation of piracetam (PCM), a nootropic drug used for memory enhancement. The addition of 1 mol% citric acid (CA) and tricarballylic acid (TA) can significantly inhibit the phase transformation of PCM Form I to Form II, while glutaric acid (GA) and adipic acid (AA) produce a minor effect. A molecular simulation shows that organic acid molecules can adsorb on the crystal surface of PCM Form I, thus slowing the movement of molecules from the metastable form to the stable form. Our study provides deeper insights into the mechanisms of solid-state polymorphic phase transformation of drugs in the presence of additives and facilitates opportunities for controlling the stability of metastable pharmaceuticals.

Elevated Mast Cell Abundance Is Associated with Enrichment of CCR2+ Cytotoxic T Cells and Favorable Prognosis in Lung Adenocarcinoma.

Mast cells constitute indispensable immunoregulatory sentinel cells in the tumor microenvironment. A better understanding of the regulation and functions of mast cells in lung adenocarcinoma (LUAD) could uncover therapeutic approaches to reprogram the immunosuppressive tumor microenvironment. Here, we performed flow cytometry and single-cell RNA sequencing (scRNA-seq) of patient LUAD samples to comprehensively characterize LUAD-infiltrating mast cells. Mast cells exhibited functional heterogeneity and were enriched in LUAD with ground-glass opacity features (gLUAD). The mast cells in gLUAD exhibited proinflammatory and chemotactic properties while those in radiologically solid LUAD (sLUAD) were associated with tumor angiogenesis. Mast cells were an important source of CCL2 and correlated with the recruitment of CCR2+ CTL, a specific subcluster of preexhausted T cells with tissue-resident memory phenotype and enhanced cytotoxicity. Increased infiltration of mast cells and CCR2+ CTLs and their colocalization showed a strong association with favorable prognosis after surgery but were not associated with improved survival after chemotherapy. Collectively, these findings reveal a key role of mast cells in LUAD and their potential cross-talk with CTLs, suggesting that targeting mast cells may be an immunotherapeutic strategy for LUAD. SIGNIFICANCE: Comprehensive characterization of mast cells in lung adenocarcinoma elucidates their heterogeneity and identifies interplay between mast cells and CCR2+ T cells that is associated with a favorable prognosis.

Functional role of frontal electroencephalogram alpha asymmetry in the resting state in patients with depression: A review.

Depression is a psychological disorder that affects the general public worldwide. It is particularly important to make an objective and accurate diagnosis of depression, and the measurement methods of brain activity have gradually received increasing attention. Resting electroencephalogram (EEG) alpha asymmetry in patients with depression shows changes in activation of the alpha frequency band of the left and right frontal cortices. In this paper, we review the findings of the relationship between frontal EEG alpha asymmetry in the resting state and depression. Based on worldwide studies, we found the following: (1) Compared with individuals without depression, those with depression showed greater right frontal EEG alpha asymmetry in the resting state. However, the pattern of frontal EEG alpha asymmetry in the resting state in depressive individuals seemed to disappear with age; (2) Compared with individuals without maternal depression, those with maternal depression showed greater right frontal EEG alpha asymmetry in the resting state, which indicated that genetic or experience-based influences have an impact on frontal EEG alpha asymmetry at rest; and (3) Frontal EEG alpha asymmetry in the resting state was stable, and little or no change occurred after antidepressant treatment. Finally, we concluded that the contrasting results may be due to differences in methodology, clinical characteristics, and participant characteristics.

Neural Stem/Progenitor Cell Transplantation in Parkinson's Rodent Animals: A Meta-Analysis and Systematic Review.

The effects of neural stem/progenitor cells (NSPCs) have been extensively evaluated by multiple studies in animal models of Parkinson's disease (PD), but the therapeutic efficacy was inconsistent. Here, we searched 4 databases (PubMed, Embase, Scopus, and Web of Science) and performed a meta-analysis to estimate the therapeutic effects of unmodified NSPCs on neurological deficits in rodent animal models of PD. Data on study quality score, behavioral outcomes (apomorphine or amphetamine-induced rotation and limb function), histological outcome (densitometry of TH+ staining in the SNpc), and cell therapy-related severe adverse events were extracted for meta-analysis and systematic review. Twenty-one studies with a median quality score of 6 (range from 4 to 9) in 11 were examined. Significant improvement was observed in the overall pooled standardized mean difference (SMD) between animals transplanted with NSPCs and with control medium (1.22 for apomorphine-induced rotation, P < .001; 1.50 for amphetamine-induced rotation, P < .001; 0.86 for limb function, P < .001; and -1.96 for the densitometry of TH+ staining, P < .001). Further subgroup analysis, animal gender, NSPCs source, NSPCs dosage, and pretreatment behavioral assessment were closely correlated with apomorphine-induced rotation and amphetamine-induced rotation. In conclusion, unmodified NSPCs therapy attenuated behavioral deficits and increased dopaminergic neurons in rodent PD models, supporting the consideration of early-stage clinical trial of NSPCs in patients with PD.

Subsolid Lesions Exceeding 3 Centimeters: The Ground-Glass Opacity Component Still Matters.

BACKGROUND: Recent studies on the favorable prognosis of ground-glass opacities (GGO) featured lung adenocarcinoma compared with solid nodules were limited to small tumors measuring 3.0 cm or less. This study investigated whether the GGO component could predict better prognosis in patients with large subsolid lesions exceeding 3 cm compared with small solid nodules within the same clinical T category. METHODS: From 2010 to 2015, 1010 patients with completely resected clinical N0 lung adenocarcinoma were enrolled, including 860 solid lesions and 150 subsolid lesions exceeding 3 cm. To analyze the prognostic significance of the GGO component, propensity score matching adjusting the solid component size was performed. RESULTS: After propensity score matching, 144 pairs of patients were analyzed. The mean size of the solid component was 23.7 mm in the GGO group and 24.4 mm in the solid group (P = .450). The GGO group had significantly better overall survival (P = .011) and recurrence-free survival (P = .003), which were also validated in patients with solid-predominant lesions. Subgroup analysis showed the GGO group was associated with better prognosis in each clinical T category. CONCLUSIONS: The prognosis of patients with GGO lesions exceeding 3 cm was better than that of patients with small solid lesions, even within the same clinical T category. Clinical T classification incorporating the GGO component may provide better prognostic prediction for patients with lung cancer exceeding 3 cm.

Clinical Features, Treatments, and Prognostic Factors of Spinal Myxopapillary Ependymoma.

OBJECTIVE: To investigate the clinical characteristics and factors affecting the prognosis of myxopapillary ependymoma (MPE). METHODS: We retrospectively analyzed the clinical data of 24 patients diagnosed with MPE who were surgically treated from January 2010 to January 2020 in the Department of Neurosurgery at Tongji Hospital (Tongji Medical School, Huazhong University of Science and Technology). RESULTS: Among the 24 included patients, there were 13 male and 11 female patients. The ages of the included patients ranged from 15 to 59 years old, with an average age of 35.2 years old. The Preoperative McCormick grade included 20 cases (83.3%) that were grade II and 4 cases (16.7%) that were grade III. The follow-up times ranged from 6 months to 10 years, with an average of 50.9 months. The Postoperative McCormick grade included 7 cases (29.2%) that were grade I, 4 cases (16.7%) that were grade II, 12 cases (50%) that were grade III and 1 case (4.2%) that was grade IV. The 1-year, 2-year, and 10-year recurrence rate was 8.3%, 29.2%, 41.7%, respectively. The 1-year, 2-year, and 10-year survival rate was 100%, 100%, 95.8% respectively. χ2 test revealed a significant difference between the degree of surgical resection (P = 0.012 < 0.05). The Kaplan-Meier method found that the degree of tumor resection (P = 0.031 < 0.05) was related to progression-free survival. The Cox analysis revealed there was no significant independent prognostic factors. CONCLUSIONS: Our findings suggest that the degree of surgical resection was a key factor that affected the prognosis and neurologic function of the included patients with MPE.

Cranial Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumors: A Retrospective Study Focused on Prognostic Factors and Long-Term Outcomes.

Purpose: Cranial Ewing sarcoma (ES)/peripheral primitive neuroectodermal tumors (pPNETs) are rarely reported because of their extremely low incidence, and the current understanding of these tumors is poor. The purpose of this study was to illustrate the clinical, radiological, and pathological features of cranial ES/pPNETs and to discuss prognostic factors by survival analysis. Methods: A total of 31 patients who were pathologically diagnosed with cranial ES/pPNETs between 2000 and 2019 were enrolled in this study. To identify which parameters were associated with higher progression-free survival (PFS) and overall survival (OS) rates, univariate and multivariate analyses were performed. Results: The mean follow-up period was 24.8 months (range, 1-109 months). Eighteen (58.1%) patients had local recurrence and seven (22.6%) patients had distant metastasis. The results of the univariate analysis suggest that the extent of resection and adjuvant radiotherapy are potential prognostic factors for PFS and OS. Adjuvant chemotherapy was associated with OS (P = 0.027) but not with PFS (P = 0.053). The multivariate analysis revealed that the extent of resection and adjuvant radiotherapy were independent prognostic factors for both PFS and OS. In addition, metastasis was an adverse prognostic factor for OS. Conclusions: Surgical management plays a crucial role in the treatment of cranial ES/pPNETs, and gross total resection should be striven for whenever possible. Post-operative radiotherapy is highly recommended to improve PFS and OS. This study also confirms that metastasis is an adverse prognostic factor for cranial ES/pPNETs.

Clinical presentation and long-term outcome of primary spinal intradural malignant peripheral nerve sheath tumors.

OBJECTIVE: Primary spinal intradural malignant peripheral nerve sheath tumors (MPNSTs) are exceedingly rare, and there is limited published information regarding these lesions. The purpose of this study was to analyze the clinical course, treatment, and outcome of primary spinal intradural MPNSTs. PATIENTS AND METHODS: A retrospective study was performed on 8 patients with primary spinal intradural MPNSTs who were surgically treated and pathologically confirmed in our institution between 2007 and 2018. RESULTS: There were 3 females and 5 males, with a median age of 46.5 years (range, 21-68 years). Limb weakness was the most common clinical symptom (5/8, 62.5%). The radiological diagnosis was meningioma or schwannoma in most patients (7/8, 87.5%). Malignancies were graded high in 5 cases (62.5%) and low in 3 cases (37.5%). Gross total resection (GTR) was performed in 5 cases, while subtotal resection (STR) was achieved in 3 cases. The mean follow-up period was 48.9 months (range, 10-160 months). During follow-up, local recurrence occurred in 6/8 cases (75.0%) and distant metastasis occurred in 2/8 cases (25.0%). The median survival time (MST) of these 8 patients was 21.0 months. The overall 1-year, 2-year, and 5-year survival rates were 87.5% (7/8), 50.0% (4/8), and 25.0% (2/8), respectively. CONCLUSIONS: Primary spinal intradural MPNST is a challenging clinical entity given its high local relapse rate. Primary spinal intradural MPNSTs radiologically present themselves heterogeneous and thus difficult to distinguish from schwannomas or meningiomas. Surgical resection, especially GTR, is the preferential treatment for primary spinal intradural MPNSTs.

Treatment Outcomes and Prognostic Factors of Patients With Primary Spinal Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumors.

Purpose: Primary spinal Ewing sarcoma (ES)/peripheral primitive neuroectodermal tumors (pPNETs) are extremely rare, and the current understanding of these tumors is poor. The authors aimed to illustrate the clinical characteristics of primary spinal ES/pPNETs and to discuss prognostic factors by survival analysis. Methods: A total of 40 patients who were pathologically diagnosed with primary spinal ES/pPNETs between 2000 and 2018 were enrolled in this study. Progression-free survival (PFS) and overall survival (OS) were estimated by the Kaplan-Meier method to identify potential prognostic factors. Factors of p ≤ 0.1 in the Log-rank tests were subjected to multivariate analysis by Cox regression analysis. Results: The mean follow-up period was 23.8 (range, 2-93) months, and 24 (60.0%) patients had local recurrence and 11 (27.5%) patients had distant metastasis. The 1-, 2-, and 5-year PFS rates were 57.7, 30.4, and 9.5%, respectively. The 1-, 2-, and 5-year OS rates were 74.8, 50.7, and 12.2%, respectively. The univariate analysis suggested that resection mode, postoperative Frankel score, adjuvant chemotherapy and adjuvant radiotherapy were potential prognostic factors for OS and PFS. However, after these factors were subjected to multivariate analyses, only adjuvant radiotherapy and resection mode remained as independent prognostic factors. Conclusions: Total en bloc resection can significantly improve PFS for primary spinal ES/pPNETs and adjuvant radiotherapy was a favorable factor for PFS. Total en bloc resection and adjuvant radiotherapy considerably improve OS for patients with primary spinal ES/pPNETs.

Clinical Features and Long-Term Outcome of Primary Intracranial Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumors: 14 Cases From a Single Institution.

OBJECTIVE: Primary intracranial Ewing sarcoma (ES)/peripheral primitive neuroectodermal tumors (pPNETs) are extremely rare, and only a few studies have reported >4 cases of this disease. The purpose of this study was to explore the clinical features, treatment, and outcome of primary intracranial ES/pPNETs. METHODS: The clinical data of 14 patients who had been surgically treated from February 2003 to November 2017 and in whom immunohistochemical staining results had confirmed the diagnosis of primary intracranial ES/pPNETs were retrospectively analyzed. Kaplan-Meier survival analysis was used to estimate the survival rate and the median survival time (MST). RESULTS: Gross total resection (GTR) was achieved in 7 cases, and subtotal resection was performed in 7 cases. During follow-up, 10 (71.4%) patients had local recurrence and 3 (21.4%) patients had distant metastasis. The overall 1-, 2-, and 5-year survival rates were 78.6%, 47.6%, and 19.0%, respectively. Kaplan-Meier survival analysis showed that postoperative radiotherapy was a significant prognostic factor for longer MST (P = 0.034). GTR and radiotherapy with or without adjuvant chemotherapy yielded the highest 2-year survival rate (100%). Three patients who underwent GTR, radiotherapy, and chemotherapy had the highest 2-year survival rates (100%) and the longest MST (48 months). CONCLUSIONS: Primary intracranial ES/pPNETs have an aggressive clinical course, with a high tendency for local recurrence and distant metastasis. Radiotherapy plays a significant role in improving the survival of patients. GTR combined with radiotherapy and chemotherapy may be the most beneficial treatment modality.