Single-cell RNA sequencing reveals the mechanism of PI3K/AKT/mTOR signaling pathway activation in lung adenocarcinoma by KRAS mutation.

BACKGROUND: Aberrant activation of the phosphatidlinositol 3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) signaling pathway has been shown to play an important role in lung adenocarcinoma (LUAD). The effect of KRAS mutations, one of the important signatures of LUAD, on the PI3K/AKT/mTOR pathway in LUAD remains unclear. METHODS: The Seurat package and principal component analysis were used for cell categorization of single-cell RNA sequencing data of LUAD. The AUCell score was used to assess the activity of the PI3K/AKT/mTOR pathway. Meanwhile, using the gene expression profiles and mutation profiles in the The Cancer Genome Atlas dataset, LUAD patients were categorized into KRAS-mutant (KRAS-MT) and KRAS-wild-types (KRAS-WT), and the corresponding enrichment scores were calculated using gene set enrichment analysis analysis. Finally, the subpopulation of cells with the highest pathway activity was identified, the copy number variation profile of this subpopulation was inscribed using the inferCNV package and the CMap database was utilized to make predictions for drugs targeting this subpopulation. RESULTS: There is higher PI3K/AKT/mTOR pathway activity in LUAD epithelial cells with KRAS mutations, and high expression of KRAS, PIK3CA, AKT1 and PDPK1. In particular, we found significantly higher levels of pathway activity and associated gene expression in KRAS-MT than in KRAS-WT. We identified the highest pathway activity on a subpopulation of GRB2+ epithelial cells and the presence of amplified genes within its pathway. Finally, drugs were able to target GRB2+ epithelial cell subpopulations, such as wortmannin, palbociclib and angiogenesis inhibitor. CONCLUSIONS: The present study provides a basic theory for the activation of the PI3K/AKT/mTOR signaling pathway as a result of KRAS mutations.

Analyzing robotic surgery impact on recovery quality & emotions.

Background: The objective of this study is to investigate the postoperative recovery quality and emotional status of patients with non-small cell lung cancer (NSCLC) who underwent robot-assisted and video-assisted thoracoscopic surgery using the 15-item Quality of Recovery (QoR-15) scale and to analyze the correlation. Methods: We collected clinical data from 320 patients with NSCLC who underwent lobectomy using either robot-assisted thoracoscopic surgery (RATS) or video-assisted thoracoscopic surgery (VATS) at our center from January 2021 to December 2022. We compared perioperative parameters and followed up after the operation using the QoR-15 scale to objectively assess the quality of postoperative recovery and physical and emotional status. Results: Apart from a notable distinction in anesthesia time, no significant differences were observed in other general data. Notably, the overall recovery rate for patients in the RATS group surpassed that of the VATS group (P < 0.05). Specifically, the recovery rates in the RATS group were significantly superior to those in the VATS group across nociceptive factors, emotional factors, activities of daily living, physiological factors, and cognitive ability (P < 0.05). Spearman correlation analysis between surgical methods and various indicators of the QoR-15 scale showed significant correlations between surgical methods (P < 0.05). Conclusion: The QoR-15 scale is a valuable tool for assessing the postoperative recovery quality in lung cancer patients. The RATS plays a significant role in promoting the swift postoperative recovery of patients and demonstrates excellent efficacy, safety, and reliability.

Diagnosis and treatment of high-risk bilateral lung ground-glass opacity nodules.

In recent years, there has been a significant increase in the detection rate of Ground Glass Opacity (GGO) nodules through high-resolution computed tomography (HRCT). GGO is an imaging finding that encompasses various pathological types, some of which exhibit indolent growth, while others may represent early lung cancer or remain relatively stable, not significantly impacting the surgical treatment outcome. In clinical practice, patients often experience psychological anxiety when multiple pulmonary GGO nodules are present, and they may request simultaneous resection. However, there is currently no standardized criterion for determining when multiple GGO nodules should be resected. As personalized medicine continues to advance, the treatment approach for multiple pulmonary GGO nodules needs to prioritize accuracy. High-risk factors associated with multiple pulmonary GGO nodules may necessitate surgical intervention along with mediastinal lymph node dissection or sampling. This article provides a review of the characteristics, treatment methods, and clinical experiences related to multiple pulmonary GGO nodules, offering practical insights and guidance for healthcare professionals.

Diagnostic value of peripheral blood eosinophils for benign and malignant pulmonary nodule.

This retrospective study aims to assess the diagnostic utility of peripheral blood eosinophil counts in distinguishing between benign and malignant pulmonary nodules (PNs) prior to surgical intervention. We involved patients presenting with PNs measuring ≤30 mm as the primary CT imaging finding prior to surgical procedures at the General Hospital of Northern Theater Command in Shenyang, China, during the period spanning 2021 to 2022. Multivariable logistic regression analysis and receiver operator characteristic curve analysis, along with area under the curve (AUC) calculations, were used to determine the diagnostic value of eosinophil. A total of 361 patients with PN were included, consisting of 135 with benign PN and 226 with malignant PN. Multivariable logistic regression analysis showed that eosinophil percentage (OR = 1.909, 95% CI: 1.323-2.844, P < .001), absolute eosinophil value (OR = 0.001, 95% CI: 0.000-0.452, P = .033), tumor diameter (OR = 0.918, 95% CI: 0.877-0.959, P < .001), nodule type (OR = 0.227, 95% CI: 0.125-0.400, P < .001), sex (OR = 2.577, 95% CI: 1.554-4.329, P < .001), and age (OR = 0.967, 95% CI: 0.945-0.989, P = .004) were independently associated with malignant PN. The diagnostic value of regression model (AUC [95% CI]: 0.775 [0.725-0.825]; sensitivity: 74.3%; specificity: 71.1%) was superior to eosinophil percentage (AUC [95% CI]: 0.616 [0.556-0.677]; specificity: 66.8%; specificity: 51.1%) (Delong test: P < .001). Peripheral blood eosinophil percentage might be useful for early malignant PN diagnosis, and combining that with other characteristics might improve the diagnostic performance.

miR-140-3p enhances the sensitivity of LUAD cells to antitumor agents by targeting the ADAM10/Notch pathway.

Background: The Notch pathway, which is related to the drug-resistance of lung adenocarcinoma (LUAD) type of non-small cell lung cancer (NSCLC) cells, is activated by cleavage of Notch proteins mediated by ADAMs, ADAM10 or ADAM17. Methods: In the present study, our results demonstrated that of these two ADAMs, the expression of ADAM10 in clinical samples of the LUAD type of NSCLC was much higher than that of ADAM17, while miR-140-3p - an miRNA that could target ADAM10 - was identified by an online tool: miRDB (miRNA database). The detail function and mechanism of miR-140-3p in regulating the sensitivity of NSCLC cells to antitumor drugs was systematically explored in vitro and in vivo. Results: In A549, a typical NSCLC LUAD cell line, miR-140-3p decreased ADAM10 expression and repressed activation of the Notch pathway by repressing cleavage of Notch proteins. The expression of miR-140-3p was negatively related to ADAM10 in clinical specimens. Nucleocytoplasmic separation/subfraction assays showed that miR-140-3p was able to inhibit the cleavage of Notch protein, and led to the accumulation of Notch intracellular domains (NICD) in the nucleus. Overexpression of miR-140-3p enhanced the sensitivity of A549 cells to antitumor agents by targeting the 3'UTR region of ADAM10 mRNA in both cultured cells and in vivo models. Conclusion: ADAM10 plays a major role in LUAD, and miR-140-3p acts on ADAM10 and inhibits its expression and the cleavage of Notch protein, leading to the inhibition the activity of the Notch pathway, and ultimately upregulating LUAD cell sensitivity to anti- tumor drugs.

Feasibility and quality control of robotic sleeve lobectomy and bronchoplasty / 中国胸心血管外科临床杂志

@#Objective    To explore the feasibility of robotic sleeve lobectomy and bronchoplasty and to summarize the experience of quality control and technical process management. Methods    From January to December 2018, our hospital completed robotic sleeve lobectomy and bronchoplasty for 5 patients, including the upper right lung lobe in 2 patients, the middle right lung lobe in 1 patient and the lower left lung lobe in 2 patients. There were 3 males and 2 females with an age of 56.6 (39-75) years. The surgical approach was the same as the surgical incision of the robotic lobectomy. During the operation, the lobes were separated, all enlarged mediastinal lymph nodes were cleaned, pulmonary hilum was dissected, pulmonary arteriovenous vessels and bronchi were exposed, and pulmonary vessels were treated. After exposing the main bronchi, the bronchi were cut off at the distal end of the lesion, and the lobes where the lesion was located (including lesions) were excised by sleeve type and the bronchi were continuously sutured with 3-0 Prolene from the back wall for anastomosis. After the anastomosis, no air leakage was found in the expanded lung, and the anastomosis was no longer wrapped. Results    The operation time was 147.4 (100-192) min, including bronchial anastomosis time 17.6 (14-25) min. Intraoperative blood loss was 60.0 (20-100) mL, and 20 (9-37) lymph nodes were dissected. Three patients had squamous cell carcinoma, 1 adenocarcinoma, and 1 neuroendocrine tumor. All patients showed negative results in the freezing pathology of bronchial stump during operation. All patients recovered well after surgery, without perioperative complications, and the anastomosis was smooth. Postoperative hospital stay was 10.8 (7-14) days. The patients were followed up for 6 to 12 months without anastomotic stenosis or other complications. Conclusion    Since the robot system is a special instrument with 3D vision and 7 degrees of freedom for movable joints, the robotic bronchial suture is more flexible and accurate. The robotic sleeve lobectomy and bronchoplasty are safe and feasible.

Preoperative localization indication of clinical peripheral pulmonary ground-glass nodules by Da Vinci robot surgery / 中国胸心血管外科临床杂志

@#Objective    To investigate the preoperative localization of pulmonary glabrous nodules. Methods    A total of 192 patients admitted to General Hospital of  Northern Theater Command from April 2012 to September 2019 were selected for the study. There were 95 males and 97 females at an age of 56.47±11.79 years. All patients completed preoperative examination, and were divided into a positioning group (n=97) and a non-positioning group (n=95) according to whether the preoperative positioning was performed. And the surgical indicators between the two groups were compared. According to the substance of ground-glass opacity, they were divided into a pure ground-glass nodules group (n=23) and a mixed ground-glass nodules group (n=74) in the positioning group and a pure ground-glass nodules group (n=14) and a mixed ground-glass nodules group (n=81) in the non-positioning group . According to the size and distance of the nodules from the pleura and whether the nodules could be detected, the corresponding linear function was obtained. Results    The operative time of methylene blue localization group was shorter than that of the no localization group. In the scatter plot, the corresponding diameter and depth of the nodules and the corresponding coordinate points which can be explored were described. And linear regression was performed on all the coordinate points to obtain the linear function: depth=0.648×diameter–1.446 (mm). It can be used as an indication for the preoperative localization of pure ground-glass nodules in Da Vinci robotic surgery. Linear function: depth=0.559 5×diameter+0.56 (mm). It can be used as an indication of preoperative localization of mixed ground-glass nodules in Da Vinci robotic surgery. Conclusion    This equation can be used as a preoperative indication for clinical peripheral pulmonary ground-glass nodules.

[Survival Analysis of Stage I Non-small Cell Lung Cancer Patients Treated with 
Da Vinci Robot-assisted Thoracic Surgery].

BACKGROUND: Da Vinci robotic surgery system is widely used in department of thoracic surgery. The aim of this study is to investigate the treatment outcome of stage I non-small cell lung cancer (NSCLC) via da Vinci Surgical System. METHODS: Clinical date of 347 stage I NSCLC patients, who underwent lobectomy and systematic node dissection from Jan. 2012 to Dec. 2017, were reviewed. 134 patients underwent robot-assisted thoracic surgery (RATS) and 213 patients underwent video-assisted thoracic surgery (VATS). To compare perioperative outcome (blood lose, postoperative drainage, drainage time, postoperative hospital stay, number of the LN dissection) and analyze overall survival (OS), disease free survival (DFS) of the two groups and prognostic factors. RESULTS: The RATS group got less blood lose [(49±39 mL for RATS vs (202±239) mL for VATS, P<0.05] and postoperative drainage [Day 1: (248±123) mL for RATS vs (350±213) mL for VATS; Day 2: (288±189) mL for RATS vs (338±189) mL for VATS, P<0.05]. There were no significant difference for drainage time (10±5 for RATS vs 11±8 for VATS, P<0.05) and postoperative hospital stay (13±6 for RATS vs 14±9 for VATS, P<0.05) between the two groups. The RATS group harvested a more number of mean stations (5±2 for RATS vs 4±2 for VATS) and amounts (18±9 for RATS vs 11±8 for VATS) of the lymph nodes, P<0.05. There was no statistically significant difference of OS between RATS and VATS group [1-year OS: 97.3% vs 96%; 3-year OS: 89.8% vs 83.1%; 5-year OS: 87.5 % vs 70.3%; overall survival time (mean): 61 months vs 59 months, P>0.05]; corresponding there had a statistically significant difference of DFS between the two groups [1-year DFS: 93.7% vs 91.3%; 3-year DFS: 87.7% vs 68.4%; 5-year DFS: 87.7% vs 52.5%; disease free survival time (mean): 61 months vs 50 months, P<0.05]. The univariate analysis found that the amounts of the lymph nodes dissection was the prognostic factor for OS and tumor diameter, surgical approach, stations and amounts of the lymph nodes dissection were respectively the prognostic factors for DFS. However, multivariate analysis found that there was not independently factors for OS, but the tumor diameter and surgical approach were independently associated with DFS. CONCLUSIONS: There was no significant difference about OS between the two groups, but the RATS got better DFS. RATS got more number of the LN dissection and less blood lose.

[A Paired Case Controlled Study Comparing the Short-term Outcomes of Da Vinci RATS and VATS Approach for Non-small Cell Lung Cancer].

BACKGROUND: Da Vinci Surgical System is one of the greatest inventions of the 20th century, which represents the development direction of the precise minimally invasive surgical techniques, the aim of this study was to comparing the short-term outcomes between da Vinci robot-assisted lobectomy and video-assisted thoracic surgery (VATS) lobectomy for non-small cell lung cancer. METHODS: 45 pairs of non-small cell lung cancer patients underwent pulmonary lobectomy with da Vinci Robotic assisted thoracoscopic (RATS) and VATS approach during the same period from January 2014 to January 2017. The operative time, estimated blood loss (EBL), total number and total groups of dissected lymph nodes, postoperative duration of drainage, the first day volume of drainage, total volume of drainage were compared. RESULTS: No perioperative death and convertion to thoracotomy occured in both groups. There were significant difference between RATS group and VATS group in EBL [(50.30±32.33) mL vs (208.60±132.63) mL], the first day volume of drainage [(275.00±145.42) mL vs (347.60±125.80) mL], the dissected total number [(22.67±9.67) vs (15.51±5.41)] and total team [(6.31±1.43) vs (4.91±1.04)] of lymph node. There were no significant difference in other outcomes. CONCLUSIONS: RATS is safe and effective and took better short-outcomes than VATS in non-small cell lung cancer.

Surgical treatment of mediastinal tumors combined with myasthenia gravis: comparison of Da Vinci robot-assisted, video-assisted thoracoscopic surgery and median sternotomy / 中国胸心血管外科临床杂志

@#Objective To compare three surgical treatments for mediastinal mass with myasthenia gravis. Methods Retrospective analysis was performed on the clinical data of 53 patients who underwent extended thymectomy between January 2010 and December 2017 in our hospital. There were 29 males and 24 females, aged 17-73 years. Patients were divided into three groups according to the surgical methods: a group A (video-assisted thoracoscopic surgery with the da Vinci robotic system, n=22), a group B (video-assisted thoracoscopic surgery, n=12) and a group C (median sternotomy, n=19). The gender distribution, age, intraoperative blood loss, operation time, postoperative extubation time, postoperative hospital stay, Osserman classification of myasthenia gravis, postoperative myasthenic remission rate, etc were compared in three groups. Results No perioperative death was observed in 53 patients. One patient in the group C suffered from postoperative myasthenic crisis and improved after active treatment. One patient with video-assisted thoracoscopic surgery was converted to median sternotomy due to the intraoperative injury of the left brachiocephalic vein. Compared with the group B and group C, the group A had shorter operation time, less intraoperative blood loss and drainage on the first postoperative day and fewer days of extubation. Postoperative hospital stay was less in the group A than that in the group C (P<0.05). The postoperative myasthenic remission rate was higher in the group A than that in the other two groups, but there was no statistical difference. Conclusion Because of the robot’s unique minimally invasive advantage, in this study, the outcome of patients with myasthenia gravis treated with Da Vinci robots and thymectomy is better than that of the remaining two groups in terms of perioperative outcomes and myasthenic remission rate. But long-term results and a large of number matching experiments are needed to confirm. However, it is undeniable that robotic surgery must be the future of the minimally invasive surgery.

[Clinical experience of the treatment of solitary pulmonary nodules with Da Vinci surgical system].

BACKGROUND: A solitary pulmonary nodule (SPN) is defined as a round intraparenchimal lung lesion less than 3 cm in size, not associated with atelectasis or adenopathy. The aim of this study is to learn clinical experience of the treatment of SPN with Da Vinci Surgical System. METHODS: A total of 9 patients with solitary pulmonary nodules (SPN) less than 3 cm in diameter was treated with Da Vinci Surgical System (Intuitive Surgical, California) in thoracic surgery department from General Hospital of Shenyang Militrary Region from November 2011 to March 2014. This group of patients included 3 males and 6 females, and the mean age was 51±9.9 yr (range: 41-74 yr). Most of the patients were no obvious clinical symptoms (7 cases were found by physical examination, others were with cough and expectoration). Their median medical history was 12 mo (range: 4 d-3 yr). All the lesions of patients were peripheral pulmonary nodules and the mean diameter of those was (1.4±0.6) cm(range: 0.8-2.8 cm). Wedge-shaped resection or lobectomy was performed depending on the result of rapid pathology and systemic lymph node dissection was done for malignant leision. We used general anesthesis with double lumens trachea cannula. We set the patients in lateral decubitus position with jackknife. The patient cart enter from top of the patient. The position of trocars would be set according to the position of lesion. A 12 mm incision was positioned at the 8th intercostal space in the posterior axillary line as vision port, and two 8 mm incisions were positioned at the 5th intercostal space between the anterior axillary line and midclavicular line, and the 8th infrascapular line as robotic instrument ports about 10 cm apart from the vision port. One additional auxiliary small incision for instrument without retracting ribs was set at the 7th intercostal space in the middle axillary line. RESULTS: There were 4 benign leisions and 5 malignancies identified. Wedge-shaped resection was performed for 4 patients, lobectomy with systemic lymph node dissection for 3 patients (including 2 right middle lobectomies and 1 left upper lobectomy) and wedge-shaped resection with systemic lymph node dissection for 2 patients of poor lung function. All of the 9 cases were completed with total robotic procedure without conversion. The pathological results included 3 inflammatory pseudotumors, 1 hamartoma, 5 adenocarcinomas. All of the 29 patients were hospital discharged smoothly. The patients were followed up for 0.1-18.5 mo (median 11 mo) without recurrence or metastasis. CONCLUSIONS: The SPN patients should be given active surgical treatments to improve the diagnose rate as well as the cure rate of early non-small cell lung cancer. Since da Vinci Surgical System is a safe and minimally invasive treatment for SPN, it has higher value to the diagnosis and treatment of SPN.