The emerging nanomedicine-based technology for non-small cell lung cancer immunotherapy: how far are we from an effective treatment.

Non-small cell lung cancer (NSCLC) is a prominent etiology of cancer-related mortality. The heterogeneous nature of this disease impedes its accurate diagnosis and efficacious treatment. Consequently, constant advancements in research are imperative in order to comprehend its intricate nature. In addition to currently available therapies, the utilization of nanotechnology presents an opportunity to enhance the clinical outcomes of NSCLC patients. Notably, the burgeoning knowledge of the interaction between the immune system and cancer itself paves the way for developing novel, emerging immunotherapies for treating NSCLC in the early stages of the disease. It is believed that with the novel engineering avenues of nanomedicine, there is a possibility to overcome the inherent limitations derived from conventional and emerging treatments, such as off-site drug cytotoxicity, drug resistance, and administration methods. Combining nanotechnology with the convergence points of current therapies could open up new avenues for meeting the unmet needs of NSCLC treatment.

A nomogram for predicting the risk of lymph node metastasis in T1-2 non-small-cell lung cancer based on PET/CT and clinical characteristics.

BACKGROUND: Accurately predicting the risk level for a lymph node metastasis is critical in the treatment of non-small cell lung cancer (NSCLC). This study aimed to construct a novel nomogram to identify patients with a risk of lymph node metastasis in T1-2 NSCLC based on positron emission tomography/computed tomography (PET/CT) and clinical characteristics. METHODS: From January 2011 to November 2017, the records of 318 consecutive patients who had undergone PET/CT examination within 30 days before surgical resection for clinical T1-2 NSCLC were retrospectively reviewed. A nomogram to predict the risk of lymph node metastasis was constructed. The model was confirmed using bootstrap resampling, and an independent validation cohort contained 156 patients from June 2017 to February 2020 at another institution. RESULTS: Six factors [age, tumor location, histology, the lymph node maximum standardized uptake value (SUVmax), the tumor SUVmax and the carcinoembryonic antigen (CEA) value] were identified and entered into the nomogram. The nomogram developed based on the analysis showed robust discrimination, with an area under the receiver operating characteristic curve of 0.858 in the primary cohort and 0.749 in the validation cohort. The calibration curve for the probability of lymph node metastasis showed excellent concordance between the predicted and actual results. Decision curve analysis suggested that the nomogram was clinically useful. CONCLUSIONS: We set up and validated a novel and effective nomogram that can predict the risk of lymph node metastasis for individual patients with T1-2 NSCLC. This model may help clinicians to make treatment recommendations for individuals.

Pulmonary contusion mimicking COVID-19: A case report.

BACKGROUND: Coronavirus disease 2019 (COVID-19) is a major public health emergency with obvious characteristics of human-to-human transmission, and there are infective asymptomatic carriers. Early identification and proper management of patients with COVID-19 are important. Features in chest computed tomography (CT) can facilitate identifying newly infected individuals. However, CT findings of some lung contusions are similar to those of COVID-19, as shown in the present case. CASE SUMMARY: A 46-year-old woman was admitted to hospital for backache and foot pain caused by a fall injury 1 d before hospitalization. She was suspected of having COVID-19, since there was a confirmed COVID-19 case near her residence. But she had no fever, cough, chest tightness, difficult breathing, nausea, vomiting, or diarrhea, etc. On physical examination, the lower posterior chest of both sides showed dullness on percussion and moist rales at the end of inspiration on auscultation. The white blood cell count and lymphocyte count were 10.88 × 109/L and 1.04 × 109/L, respectively. CT performed on February 7, 2020 revealed that both lungs were scattered with patchy ground-glass opacity. The patient was diagnosed with pulmonary contusion with thoracic spinal fracture (T12), calcaneal fracture, and pelvic fracture. On day 9 after conservative treatment, her condition was alleviated. On review of the chest CT, the previous shadows were significantly reduced. CONCLUSION: Differential diagnosis of lung contusion and COVID-19 must be emphasized. Both conditions require effective prompt actions, especially COVID-19.

Perioperative outcomes and mid-term effects in performing video-assisted thoracoscopic extended thymectomy for myasthenia gravis: subxiphoid versus right thoracic approaches.

BACKGROUND: Approaches of thoracoscopic thymectomy for myasthenia gravis (MG) are debatable. The subxiphoid approach is widely utilized recent years for its better visualization of the anterior mediastinum. In the present study, we compared perioperative outcomes and mid-term effects of the extended thymectomy for MG between the subxiphoid approach and the routine right-thoracic approach. METHODS: One hundred and thirty-one MG patients treated with thoracoscopic extended thymectomy were analyzed. Among them, 68 patients were operated on via the subxiphoid approach and the other 63 via the conventional right-side unilateral approach. The patient outcomes were retrospectively reviewed and evaluated. Mid-term clinical outcome was assessed according to the classification system proposed by the Myasthenia Gravis Foundation of America (MGFA). Clinical efficacy and variables influencing outcome were evaluated by the Kaplan-Meier method and Cox proportional hazards regression analysis. RESULTS: Compared with the right thoracic approach, the duration of the procedure via the subxiphoid approach was significantly shorter (P=0.035), the rates of total thymectomy were higher (P=0.028), and the pain scores on postoperative days 1, 3, and 7 were significantly lower (P<0.001, P<0.001, and P=0.03, respectively). A total of 112 patients with MG were followed up. The subxiphoid approach group reported higher rates of complete stable remission (CSR) and effective treatment of MG, although these differences were not statistically significant (Z=-0.484, P=0.627). By multivariate Cox proportional hazards modes analysis, the chance of CSR was significantly increased when age <40 (OR: 2.623, 95% CI: 1.150-5.983, P=0.022), non-thymomatous MG (OR: 1.078, 95% CI: 1.101-3.316, P=0.021) and MGFA clinical classification (OR: 2.024, 95%:1.164-3.523, P=0.013). CONCLUSIONS: The subxiphoid approach has shorter operation time, higher rates of total thymectomy and better quality of life compared with the lateral thoracoscopic approach. Preoperative age, pathological diagnoses and MGFA Clinical Classification are the independent risk factors for non-complete stable remission (NCSR) after thymectomy.

The safety of thymic vein sealing with ultrasonic energy in video-assisted thoracoscopic surgery thymectomy.

BACKGROUND: The key for conducting thymectomy by thoracoscope is the treatment of thymic veins, as they are the most common source of bleeding. The traditional treatment is to cut off the distal and proximal vessels after Ham-Lock clamping. Our team found that it is safe and reliable to use ultrasonic energy to cut off thymic veins in previous open operations. This study aimed to investigate the feasibility and safety of thymic vein sealing with ultrasonic energy in video-assisted thoracoscopic surgery (VATS) thymectomy. METHODS: A total of 169 patients with or without thymic tumors who underwent thymectomy by thoracoscope were enrolled in the study. Among them, group A, with 89 patients, underwent thoracoscopic thymic vein resection by Ham-Lock, and group B, with 80 patients, did so by ultrasonic energy. The groups were compared in terms of the characteristics of patients, tumors, and perioperative period. RESULTS: There were no significant differences in patients' characteristics between the two groups (P>0.05). There was no significant difference between the two groups in blood transfusion, operation time, drainage, and hospitalization (P>0.05). There were no deaths, secondary operation and post-operative blood transfusion, and no serious complications leading to prolonged hospitalization. One patient in group A was converted to thoracotomy due to left anonymous venous hemorrhage, and one patient in group B had thymic venous hemorrhage, but the hemorrhage was successfully stopped under thoracoscope. CONCLUSIONS: In VATS thymectomy (with or without thymic tumors), there is no significant difference in the treatment of thymic veins between Ham-Lock clipping and ultrasonic energy in conversion to open surgery in regards to thymic venous hemorrhage, postoperative drainage, blood transfusion, operation time, drainage, and hospital stay. Use of ultrasonic energy is a safe and reliable method for thymic vein disconnection.

Wnt3a Expression Is Associated with Epithelial-Mesenchymal Transition and Impacts Prognosis of Lung Adenocarcinoma Patients.

Background: Epithelial-mesenchymal transition (EMT) plays an important role in the invasion and migration during cancer metastasis. Wnt3a is one of the ligands in canonical Wnt/ß-catenin signaling pathway, which contributes to the carcinogenesis and progression of lung cancer cell lines. The aim of this study was to evaluate the association between Wnt3a and EMT-related proteins (E-cadherin and N-cadherin), and to further investigate its impact on prognosis of lung adenocarcinoma patients. Methods: A total of 147 lung adenocarcinoma patients were included and their clinicopathological characteristics were collected in this retrospective study. The expression levels of Wnt3a, E-cadherin and N-cadherin in post-surgery cancerous and adjacent normal tissues were assessed by immunohistochemistry. The association between Wnt3a and EMT-related proteins and their prognostic values were systematically evaluated. HCC827 and PC9 cell lines were treated with Wnt3a to detect the expression of EMT-related and Wnt/ß-catenin signaling-associated proteins, as well as the in vitro migration and invasion abilities. Results: High Wnt3a expression level was significantly associated with low E-cadherin (P<0.001) and high N-cadherin (P<0.001) expression levels in lung adenocarcinoma tissues. Besides, high Wnt3a level predicted poorer lung adenocarcinoma survival by univariate Cox analysis (P=0.001), while the multivariate result was not significant (P=0.355). Subgroup analysis suggested that the prognostic value of Wnt3a expression level was significant in stage T1-T2 (log rank P=0.003) and stage N0 (log rank P=0.031) patients. The multivariate Cox analysis suggested N-cadherin was an independent prognostic factor for lung adenocarcinoma patients (P=0.012). After including these markers into a nomogram, the Harrell's C-index of the nomogram was 0.755. The decision-curve analysis of our nomogram performed net benefit at the threshold probability from 21.6% to 82.0%, and the current model had a better prognostic value than TNM-classification with a lower Akaike information criterion (AIC) value of 166.54. In vitro experiments suggested that Wnt3a could regulate EMT-related proteins and promotes in vitro invasion and migration abilities. Conclusions: Wnt3a could regulate EMT-related proteins and promote the migration and invasion process of lung adenocarcinoma. Although its value as an independent prognostic factor was limited, the combined model suggested good prognostic performance for lung adenocarcinoma patients.

Sublobar Resection for Pulmonary Aspergilloma: A Safe Alternative to Lobectomy.

BACKGROUND: This study was performed to evaluate the effectiveness of sublobar resection for the treatment of pulmonary aspergilloma compared with lobectomy. METHODS: Patients with pulmonary aspergilloma who underwent lobectomy or sublobar resection in our department between March 2007 and December 2015 were retrospectively reviewed. Data were collected for patient demographic characteristics, medical history, preoperative investigations, perioperative findings, postoperative conditions, and recurrence status. Propensity-matched comparative analyses were performed to adjust for potential differences of patients' baseline characteristics between the groups. RESULTS: A total of 96 patients underwent lobectomy, 46 patients underwent attempted sublobar resection. The median follow-up time is 53 months. No recurrence was found in either group. Three patients (3.1%) in the lobectomy group required reoperation for bleeding. The patients who underwent sublobar resection had less underlying lung disease (p = 0.031), smaller lesions (p = 0.033), and were more likely to have been treated with video-assisted thoracic surgery (p < 0.001). These differences were eliminated by propensity score matching (46 pairs were successfully matched). Comparative analyses in matched groups demonstrate that there was no marked difference in the volume and duration of chest drainage or the length of postoperative hospital stay. However, the patients with sublobar resection had shorter operation time (p = 0.004), less blood loss (p = 0.042), and less postoperative complication (p = 0.048). CONCLUSIONS: Sublobar resection performed for small simple pulmonary aspergilloma and selected complex pulmonary aspergilloma has a low recurrence rate and confers perioperative advantages compared with lobectomy.

Clinical, cellular, and bioinformatic analyses reveal involvement of WRAP53 overexpression in carcinogenesis of lung adenocarcinoma.

Lung cancer, of which non-small cell lung cancer accounts for 80%, remains a leading cause of cancer-related mortality and morbidity worldwide. Our study revealed that the expression of WD repeat containing antisense to P53 (WRAP53) is higher in lung-adenocarcinoma specimens than in specimens from adjacent non-tumor tissues. The prevalence of WRAP53 overexpression was significantly higher in patients with tumor larger than 3.0 cm than in patients with tumor smaller than 3.0 cm. The depletion of WRAP53 inhibits the proliferation of lung-adenocarcinoma A549 and SPC-A-1 cells via G1/S cell-cycle arrest. Several proteins interacting with WRAP53 were identified through co-immunoprecipitation and liquid chromatography/mass spectrometry. These key proteins indicated previously undiscovered functions of WRAP53. These observations strongly suggested that WRAP53 should be considered a promising target in the prevention or treatment of lung adenocarcinoma.

Downregulation of RUVBL1 inhibits proliferation of lung adenocarcinoma cells by G1/S phase cell cycle arrest via multiple mechanisms.

Lung cancer remains a leading cause of cancer-related mortality and morbidity worldwide, of which non-small cell lung cancer (NSCLC) accounts for 80 %. RUVBL1 is a highly conserved eukaryotic AAA+ adenosine 5'-triphosphatase (ATPase) that has many functions highly relevant to cancer. We therefore attempted to determine the potential role of RUVBL1 in the biogenesis of lung adenocarcinoma and obtained some interesting results. Our study revealed that RUVBL1 expression was higher in lung adenocarcinoma specimens than in those of adjacent non-tumor tissues and in lung cancer cell lines than in normal lung cell lines. RUVBL1 knockdown via siRNA reduced proliferation and caused G1/S phase cell cycle arrest in lung adenocarcinoma cell lines. The G1/S phase cell cycle arrest triggered by RUVBL1 downregulation could be attributed, at least in part, to repression of the AKT/GSK-3ß/cyclin D1 pathway and probably to the activation of IRE1α-mediated endoplasmic reticulum (ER) stress. We thus demonstrated for the first time that a knockdown of RUVBL1 could effectively inhibit the proliferation of lung adenocarcinoma A549 and H292 cells through the induction of G1/S phase cell cycle arrest via multiple mechanisms. These observations strongly suggested that RUVBL1 should be considered a promising target for the prevention or therapy of lung adenocarcinoma.