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How to improve the performance of circulating tumor DNA (ctDNA) signal acquisition and the accuracy to authenticate ultra low-frequency mutation are major challenges of minimal residual disease (MRD) detection in solid tumors. In this study, we developed a new MRD bioinformatics algorithm, namely multi-variant joint confidence analysis (MinerVa), and tested this algorithm both in contrived ctDNA standards and plasma DNA samples of patients with early non-small cell lung cancer (NSCLC). Our results showed that the specificity of multi-variant tracking of MinerVa algorithm ranged from 99.62% to 99.70%, and when tracking 30 variants, variant signals could be detected as low as 6.3 × 10 -5 variant abundance. Furthermore, in a cohort of 27 NSCLC patients, the specificity of ctDNA-MRD for recurrence monitoring was 100%, and the sensitivity was 78.6%. These findings indicate that the MinerVa algorithm can efficiently capture ctDNA signals in blood samples and exhibit high accuracy in MRD detection.
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Humans , Carcinoma, Non-Small-Cell Lung/genetics , Lung Neoplasms/genetics , Neoplasm, Residual/pathology , Biomarkers, Tumor/genetics , Computational BiologyABSTRACT
@#Objective To verify the feasibility and accuracy of the "lung surface intersegmental constant proportion landmarks", developed by our center, in identifying intersegmental planes during pulmonary segmentectomy. Methods We prospectively enrolled the patients who planned to receive thoracoscopic segmentectomy in West China Hospital of Sichuan University and The Third People's Hospital of Chengdu from September 2021 to October 2021. We took a relatively objective and feasible method, intravenous injection of indocyanine green, in identifying intersegmental planes as standard control. We intraoperatively judged the consistency between "lung surface intersegmental constant proportion landmarks" and intravenous injection of indocyanine green in identifying intersegmental planes. We discerned main landmarks of intersegmental plane by the constant proportion segment module, which was built based on the "lung surface intersegmental constant proportion landmarks", as well as distinguished the planes with discrepant fluorescence by peripheral intravenous indocyanine green injection. When the distance between the landmarks determined by the "ung surface intersegmental constant proportion landmarks" and the segmental boundaries displayed by indocyanine green fluorescence staining was ≤1 cm, the landmarks were judged to be consistent with the planes with discrepant fluorescence. As long as one of the landmarks was judged to be consistent, the method was considered to be feasible and accurate. Results 聽 聽 A total of 21 patients who underwent thoracoscopic segmentectomy were enrolled, with 5 male and 16 female patients. The median age was 55 years, ranging from 34 to 76 years. A total of 11 patients received left-side surgery, while 10 patients received right-side surgery. In the operations of 21 pulmonary segmentectomies, at least one intersegmental landmark determined by the "lung surface intersegmental constant proportion landmarks" was consistent with the intersegmental plane determined by indocyanine green fluorescence staining in each patient. Conclusion 聽 聽The intersegmental landmarks determined by the "lung surface intersegmental constant proportion landmarks" are consistent with that determined by indocyanine green fluorescence staining. The method of "lung surface intersegmental constant proportion landmarks" is feasible and accurate in identifying intersegmental planes during pulmonary segmentectomy.
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@#Objective To summarize the perioperative and long-term outcomes of ground-glass opacity (GGO) dominant early stage lung cancer patients treated by anatomic segmentectomy. Methods We collected clinical data of 756 patients from Western China Lung Cancer Database, who underwent intentional anatomic segmentectomy [tumor size (T) ≤ 2 cm, GGO ≥ 50%] in the Department of Thoracic Surgery, West China Hospital, Sichuan University from 2009 to 2018. There were 233 males and 523 females at a median age of 53 (25-83) years including 290 (38.4%) patients of simple segmentectomy and 466 (61.6%) patients of complex segmentectomy. All patients were diagnosed as adenocarcinoma, including 338 (44.7%) patients of minimally invasive adenocarcinoma and 418 (55.3%) patients of invasive adenocarcinoma. Results The median operative time was 115 (38-300) min, the median blood loss was 20 (5-800) mL, 58 (7.7%) patients had postoperative complications and the postoperative stay was 4 (2-24) days. The median follow-up period was 43.0 (30.1-167.9) months. Five-year overall survival rate was 99.5% [95%CI (98.8%, 100.0%)], 5-year recurrence-free survival rate was 98.8% [95%CI (97.5%, 100.0%)], and 5-year lung cancer-specific survival rate was 100.0%. Conclusion Anatomic segmentectomy has favorable perioperative outcomes and excellent prognosis in GGO dominant early stage lung cancer patients.
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@#Objective To identify the risk factors for postoperative recurrence of peripheral solid small-nodule lung cancer (PSSNLC) (T≤2 cm), and to explore the effects of surgery types on prognosis. Methods We extracted data from Western China Lung Cancer Database (WCLCD), a prospectively maintained database at the Department of Thoracic Surgery, West China Hospital, Sichuan University, and Surveillance, Epidemiology, and End Results (SEER) database for peripheral solid small-nodule lung cancer patients (T≤2 cm N0M0, stageⅠ) who underwent surgery between 2005 and 2016. We used univariable and multivariable logistic regression to analyze risk factors for recurrence of PSSNLC. We applied propensity-score matching to compare the long-term results of segmentectomy and lobectomy, as well as the survival of patients from WCLCD and SEER. We finally included 4 800 patients with PSSNLC (T≤2 cm N0M0)(WCLCD: SEER=354∶4 446). We matched 103 segmentectomies and 350 lobectomies in T≤1 cm, and 280 segmentectomies and 1 067 lobectomies in 1 cm<T≤2 cm at a ratio of 1∶4 according to the propensity scores. Results The results of multivariable logistic regression showed that older age (HR=1.04, 95%CI 1.03-1.05, P<0.001), male (HR=1.60, 95%CI 1.37-1.88, P<0.001), squamous carcinoma (HR=1.65, 95%CI 1.40-1.95, P<0.001), lymph node removed (HR=0.97, 95%CI 0.96-0.99, P<0.001) were risk factors for recurrence after surgery. We found that segmentectomy and lobectomy could reach similar survival in PSSNLC patient with either T≤1 cm or 1 cm<T≤2 cm. Analyses of 1 441 patients with PSSNLC after matching (WCLCD∶SEER=325∶1 116) indicated that the 5-year overall survival rate of the patients in WCLCD was better than that in SEER database ( 89.8% vs. 77.1%, P<0.001). Conclusion Older age, male, squamous carcinoma, and lymph node removed are the risk factors for recurrence of PSSNLC. Segmentectomy shows similar survival in PSSNLC patient with either T≤1 cm or 1 cm<T≤2 cm N0M0. The patients in the WCLCD shows better survival compared with of the patients in the SEER database.
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@#This patient was a 47-year female who underwent carinal resection and reconstruction because of left main bronchial mucoepidermoid carcinoma. She underwent four cycles chemotherapy when recovering from surgery because of subcarinal lymph node metastasis. However, the patient suffered from recurred productive cough and dyspnea during chemotherapy. Bronchoscopic assessment revealed stenosis at the reconstructed carina and left main bronchus five months after surgery. The granulation tissues of the left main bronchus showed no evidence of cancer recurrence. After repeated bronchoscopic resection of granulation tissue combined with bronchial stent placement, the left main bronchial stenosis gradually worsened with granulation tissue growth. Three acid-fast bacilli were found in the granulation tissue harvested ten months after surgery. The reason of postoperative bronchostenosis was confirmed as endobronchial tuberculosis, and antitubercular agents were added. Unfortunately, she had persistent left main bronchostenosis due to irreversible destruction and left pulmonary atelectasis thereafter. Therefore, for the recurring anastomotic granulomas after tracheobronchial reconstruction, the possibility of tuberculosis infection should be considered.
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@#Objective To analyze the perioperative outcomes of uniportal thoracoscopic lobectomy compared with three-port thoracoscopic lobectomy. Methods Data were extracted from the Western China Lung Cancer Database, a prospectively maintained database at the Department of Thoracic Surgery, West China Hospital, Sichuan University. Perioperative outcomes of the patients who underwent uniportal or three-port thoracoscopic lobectomy for lung cancer during January 2014 through April 2021 were analyzed by using propensity score matching. Altogether 5 817 lung cancer patients were enrolled who underwent thoracoscopic lobectomy (uniportal: 530 patients; three-port: 5 287 patients). After matching, 529 patients of uniportal and 1 583 patients of three-port were included. There were 529 patients with 320 males and 209 females at median age of 58 (51, 65) years in the uniportal group and 1 583 patients with 915 males and 668 females at median age of 58 (51, 65) years in the three-port group. Results Uniportal thoracoscopic lobectomy was associated with less intraoperative blood loss (20 mL vs. 30 mL, P<0.001), longer operative time (115 min vs. 105 min, P<0.001) than three-port thoracoscopic lobectomy. No significant difference was found between the two groups regarding the number of lymph node dissected, rate of conversion to thoracotomy, incidence of postoperative complication, postoperative pain score within 3 postoperative days, length of hospital stay, or hospitalization expenses. Conclusion Uniportal video-assisted thoracoscopic lobectomy is safe and effective, and the overall perioperative outcomes are comparable between uniportal and three-port strategies, although the two groups show differences in intraoperative blood loss.
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@#Objective To compare the perioperative outcomes of subxiphoid robot-assisted extended thymectomy (SRAET) and video-assisted thoracoscopic extended thymectomy (VATET) for myasthenia gravis complicated with thymoma. Methods Retrospective analysis of 61 patients with myasthenia gravis combined with thymoma who were admitted to the Department of Thoracic Surgery, West China Hospital, Sichuan University from January 2017 to June 2019 was performed. All patients underwent extended thymectomy, and the patients were divided into a SRAET group and a VATET group. There were 26 patients in the SRAET group, including 11 males and 15 females, with an average age of 42.20±13.20 years. There were 35 patients in the VATET group, including 14 males and 21 females, with an average age of 45.00±13.00 years. The perioperative outcomes of the two groups including gender, age, operation time, intraoperative blood loss, conversion rate, postoperative drainage, tube removal time, drainage volume, visual analogue scale, hospital stay and postoperative complications were compared. Results There was no conversion to thoracotomy, death or myasthenia crisis in both groups. The operation time (111.42±28.60 min vs. 103.71±26.20 min, P=0.845), intraoperative blood loss (32.31±23.84 mL vs. 63.57±132.22 mL, P=0.239), visual analogue scale at postoperative 24 h (2.46±0.76 vs. 2.40±0.74, P=0.751) and postoperative 48 h (2.12±0.77 vs. 2.26±0.56, P=0.407), complication rate (3.8%vs. 2.9%, P=0.675), drainage volume (206.85±130.09 mL vs. 276.86±173.46 mL, P=0.089) and hospital stay (5.81±2.52 d vs. 5.29±2.17 d, P=0.642) were not significantly different between the two groups. The visual analogue scale of the SRAET group at postoperative 72 h (1.12±0.65 vs. 1.86±0.91, P=0.001) was significantly lower than that of the VATET group. Conclusion SRAET is a safe and feasible method with less postoperative short-term pain, which is an alternative surgical treatment for myasthenia gravis complicated with thymoma.
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@#The severe situation of the spread of novel coronavirus pneumonia (COVID-19) poses a huge challenge to the admission and management of patients undergoing selective thoracic surgery. In order to ensure that patients can receive surgical treatment in time, and we can effectively prevent the outbreak and spread of the disease in the surgical department, the department should comb the relevant content from multiple aspects in accordance with the specific situation. It is necessary to adopt a new admission process of patients undergoing selective surgery and COVID-19 investigation process for patients and their families during the epidemics. We should improve the companion and suspected patient management system during the epidemic. Patients who are planning to undergo surgery need to be strictly checked for COVID-19 infection before surgery. The treatment and management strategies of patients undergoing thoracic surgery in our department are summarized in this paper.
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The epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) and programmed death receptor 1 (PD-1)/programmed death ligand 1 (PD-L1) immune checkpoint inhibitors were landmarks in the treatment of non-small cell lung cancer (NSCLC). However, the regulation mechanisms of PD-L1 expression were not fully clear in NSCLC patients with EGFR mutations. Multiple signaling pathways may be involved in the tumorigenesis regulation. This paper summarized and reviewed the potential EGFR mutations impacting on PD-L1 expression with aims to the development of strategies on immunochemical therapy for NSCLC. .
Subject(s)
Humans , Adenocarcinoma of Lung , Genetics , Pathology , B7-H1 Antigen , Metabolism , ErbB Receptors , Genetics , Gene Expression Regulation, Neoplastic , Mutation , Signal Transduction , GeneticsABSTRACT
Objective@#To study the current development of thoracic surgery in China.@*Methods@#Chinese Society for Thoracic and Cardiovascular Surgery and Chinese Association for Thoracic Surgeons jointly conducted a network survey to directors of thoracic surgery departments in the tertiary hospitals in China from November to December 2018. The contents of the survey included the basic information of the hospital and the status of thoracic surgery department in the hospital. Rank sum test was used to compare the data between different regional hospitals@*Results@#A total of 636 tertiary hospitals participated in the survey. The total number of beds for thoracic surgery departments was 30 646, with M(QR) of 40(20) (range: 3 to 393) for each hospital. The total number of thoracic surgeons was 6 747, with M(QR) of 9(6) (range: 1 to 75) in each hospital. In 2015, a total of 312 425 operations were performed in the 636 hospitals, with M(QR) of 268(484.5) (range: 4 to 8 320) for each hospital. The total number of lung cancer surgeries was 146 601 in 2015, with M(QR) of 100(216) (range: 0 to 6 911) operations in each hospital. The total number of esophageal cancer operations was 67 076, with M(QR) of 40(95) (range: 0 to 1 550) in each hospital. Minimal invasive thoracic surgery was performed in 94.3% (601/636) of the hospitals, with 86.6% (551/636) of hospitals carried out video-assisted thoracoscopic (VATS) lobectomy. Among the hospitals performing VATS lobectomy, 89.3% (492/551) of them started to perform the technique after 2006, and 93.1% (513/551) of them do single-direction thoracoscopic lobectomy. A total of 403 640 VATS lobectomies had been performed until 2015, including 163 682 cases of single-direction thoracoscopic lobectomy. In 2015, 73.74% (108 116/146 601) lung cancer operations and 37.44% (25 110/67 076) of esophageal cancer resections were performed by minimally invasive technique. The development level of hospitals among eastern, middle and Western China was different significantly on number of doctors, number of total operations, number of lung cancer surgeries, proportion of minimally invasive lung cancer surgery, number of esophageal cancer surgeries, and proportion of minimally invasive esophageal cancer surgery (χ2∶7.65 to 60.8, all P<0.05).@*Conclusions@#The discipline of thoracic surgery, especially the minimally invasive thoracic surgery in China is now experiencing a rapid development. The proportion of minimally invasive lung cancer surgery is higher than that of in the developed countries. However, unbalanced development among different regions is still a great challenge in China.
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The technique of thoracoscopic lung surgery has gradually matured. Nowadays, thoracoscope is recommended as the most preferred approach for surgical treatment of early stage non-small cell lung cancer in different guidelines. However, there are still some cases of accidential major bleeding due to vascular injury during thoracoscopic lung surgery. The wall of the hilum vessels is relatively thin. These vessels often involve a great portion of the cardiac output blood flow. Once the injury happened, the emergent condition may be life-threatening due to massive blood loss. Therefore, this became an important factor which hindered the development of thoracoscopic lung surgery. In this review, details of the vascular injury in thoracoscopic lung surgery were summarized, including the incidence of vascular injury, commonly injured sites and reasons of the injuries. Among all the cases of thoracoscopic major pulmonary resection, 2.9% to 9.2% may suffer from vascular injury during the operation. The most commonly injuried sites are pulmonary artery and the branches, and this is also the most critical situation during thoracoscopic lung surgery. Hilum adhesion is the most important risk factor for vascular injury. On the one hand, the suction-compressing angiorrhaphy technique was developed for bleeding control and angioplasty. On the other hand, the strategies like pre-control of the pulmonary, cut the bronchus in advance, and fire the bronchus and pulmonary artery together may decrease the incidence of vascular injury in patients with risk factors.