Circulating tumor cells prior to initial treatment is an important prognostic factor of survival in non-small cell lung cancer: a meta-analysis and system review.

BACKGROUND: Our study aimed to verify the prognostic value of circulating tumor cells (CTCs) prior to initial treatment on survival of non-small cell lung cancer (NSCLC) by using meta-analysis and system review of published studies. MATERIALS AND METHODS: The PubMed, EMBASE and Cochrane Library were searched, respectively, to identify all studies that addressed the issues of CTCs prior to initial treatment and progression-free survival (PFS) and overall survival (OS). Finally, ten citations were included for analysis and assessment of publication bias by using review manager 5.3 statistical software and STATA 15.0. RESULTS: Randomized model analyzing multivariate Cox Proportional Hazards Regression indicated that higher abundance of CTCs significantly predicts poorer prognosis of lung cancer cases basing both on PFS (Z = 2.31, P = 0.02) and OS of advanced cases (Z = 2.44, P = 0.01), and systematic study aslo indicated the similar results. CONCLUSION: High CTCs prior to initial treatment can predict shorter PFS and OS in NSCLC, and further studies are warranted in the future.

Combination of electromagnetic navigation bronchoscopy-guided biopsy with a novel staining for peripheral pulmonary lesions.

BACKGROUND: The diagnosis of peripheral pulmonary lesions (PPLs) is a challenging task for pulmonologists, especially for small PPLs. Conventional localization of these small PPLs, which are > 1 cm away from the visceral pleura in operation, is quite difficult. Currently used methods inevitably damage the visceral pleura and may cause a series of complications, such as pneumothorax and hemothorax. Hence, the present study aimed to find out an intraoperative localization method with no damage to the visceral pleura. METHODS: We retrospectively reviewed 21 patients with PLLs who underwent electromagnetic navigation bronchoscopy (ENB)-guided biopsy plus a new methylene blue staining with the help of massage (Massage Staining) in our department between August 2017 and December 2018. RESULTS: The median age of these 21 patients was 51.3 ± 2.1 years. The diameter of the PPLs was 8.2 ± 2.3 mm. The rate of successful biopsy was 76.2%, and the rate of excellent or satisfactory of Massage Staining was 81.0%, while all lesions of these 21 cases were included in the range of staining, and the median distance from the edge of the stained site to the edge of the lesion was 29 ± 18 mm. The duration of ENB-guided biopsy plus Massage Staining was 26.7 ± 5.3 min, and the intraoperative blood loss was 3.3 ± 1.5 ml. No pneumothorax, hemorrhage, and tracheal injury occurred intraoperatively. CONCLUSIONS: The ENB-guided biopsy combined with Massage Staining is an innovative one-stop strategy designed to enhance the precision of thoracic surgery. The Massage Staining avoids damage to the visceral pleura, causes the low incidence of complications, but yields precise localization of PPLs.

Predictive factors of prolonged mechanical ventilation, overall survival, and quality of life in patients with post-thymectomy myasthenic crisis.

BACKGROUND: Thymectomy is the primary approach for the treatment of myasthenia gravis (MG). This retrospective study aimed to identify the clinical and demographical features that may impact the duration of mechanical ventilation (DMV), the long-term survival, and the quality of life (QOL) in patients with post-thymectomy myasthenic crisis (PTMC). METHODS: We reviewed the patients who suffered from PTMC from June 2008 to November 2015. Cox proportional hazard regression analysis was used to identify potential prognostic factors that may impact DMV and long-term survival. Spearman bivariate correlation analysis was used to analyze the relationship between DMV and QOL. Statistical powers were calculated. RESULTS: In total, 70 patients with PTMC were enrolled. Alcohol abuse, high scores of Myasthenia Gravis Foundation of America (MGFA) classification and Clavien-Dindo classification were critical factors that remarkably delayed early extubation. High scores of Osserman's classification, MGFA classification, and Clavien-Dindo classification predicted a poor prognosis in PTMC patients. Occupational skills and job status were observed to be negatively affected in PTMC patients. CONCLUSIONS: To decrease the duration of mechanical ventilation, we suggest alcohol abstinence before the operation, appropriate preoperative treatment to decrease MGFA classification, and greater attention to the treatment of postoperative complications.

Surgical treatment of severe benign tracheal stenosis.

OBJECTIVE: To present clinical experiences regarding surgical treatment of patients with severe cicatricial tracheal stenosis. PATIENTS AND METHODS: From January 2008 to March 2020, 14 patients underwent tracheal resection and reconstruction under general anesthesia. Nine cases had cervical tracheal stenosis and five cases had thoracic tracheal stenosis. The mean diameter and length of strictured trachea was 0 - 8 mm with a mean of 4.5 ± 2.4 mm and 1 - 3 cm with a mean of 1.67 ± 0.63 cm, respectively. General anesthesia and mechanical ventilation were performed in ten cases and four patients underwent femoral arteriovenous bypass surgery due to severe stenosis. End-to-end anastomosis of trachea was performed in 13 cases and the anastomosis between trachea and cricothyroid membrane was performed in one case. Absorbable and unabsorbable sutures were used for the anterior and posterior anastomoses, respectively. Postoperative neck anteflexion was maintained by a suture between the chin and superior chest wall. The relevant data of the 14 patients were retrospectively reviewed, and the operation time, blood loss, postoperative hospital stay, postoperative complications and follow-up were retrieved. RESULTS: There was no intraoperative death. The length of resected trachea ranged from 1.5 to 4.5 cm with a mean of 1.67 ± 0.63 cm. Operation time ranged from 50 - 450 min with a mean of 142.8 ± 96.6 min and intraoperative hemorrhage ranged from 10 - 300 ml with a mean of 87.8 ± 83.6 ml. Follow-up period ranged from 5 to 43 months with a mean of 17.9 ± 10.6 months. None of the patients had recurrent laryngeal nerve paralysis during postoperative follow-up. Ten cases were discharged uneventfully. Anastomosis stenosis occurred in three cases who received interventional therapies. Bronchopleurocutaneous fistula occurred in one patient after 6 days postoperatively and further treatment was declined. CONCLUSION: The strategies of anesthesia, mechanical ventilation, identification of stenosis lesion, the "hybrid" sutures and postoperative anteflexion are critical to be optimized for successful postoperative recovery.

Multi-center experience in an optimized right upper lobectomy surgical procedure in China.

BACKGROUND: This multi-center study was aimed at retrospectively evaluating the feasibility, safety, clinical outcomes, and surgical learning curve of an optimized procedure for right upper lobectomy (RUL), which is challenging because of the anatomical structures and features of this lobe. METHODS: This study included 45 RUL cases of robot-assisted thoracoscopy (RATS) in a pilot cohort and 187 RUL cases of video-assisted thoracoscopy (VATS) in three cohorts. A total of 121 and 111 patients underwent traditional and optimized RUL, respectively. The optimized surgical procedure was performed to consecutively transect the superior arterial trunk and bronchus, and finally disconnect the pulmonary vein and posterior ascending artery with interlobar fissures. Clinical and radiological data were reviewed retrospectively. RESULTS: Optimized RUL can be performed successfully by RATS or VATS. The optimized procedure yielded better clinical outcomes than the traditional procedure, including shorter operation times, less blood loss, fewer complications, shorter hospital times, lower costs, and a lower likelihood of postoperative intermedius bronchial kinking. Additionally, for calcified interlobar lymph nodes, the optimized VATS group was less likely to be converted to thoracotomy than the traditional group. The skills required to perform optimized VATS RUL can be gained by surgeons after 12 to 15 cases. The two RUL procedures in the pilot cohort showed similar disease-free survival. CONCLUSIONS: The optimized RUL was safe, economical, and feasible, with a short learning curve and satisfactory disease-free survival.

Airway Microbiota in Patients With Synchronous Multiple Primary Lung Cancer: The Bacterial Topography of the Respiratory Tract.

Microbes and microbiota dysbiosis are correlated with the development of lung cancer; however, the airway taxa characteristics and bacterial topography in synchronous multiple primary lung cancer (sMPLC) are not fully understood. The present study aimed to investigate the microbiota taxa distribution and characteristics in the airways of patients with sMPLC and clarify specimen acquisition modalities in these patients. Using the precise positioning of electromagnetic navigation bronchoscopy (ENB), we analyzed the characteristics of the respiratory microbiome, which were collected from different sites and using different sampling methods. Microbiome predictor variables were bacterial DNA burden and bacterial community composition based on 16sRNA. Eight non-smoking patients with sMPLC in the same pulmonary lobe were included in this study. Compared with other sampling methods, bacterial burden and diversity were higher in surface areas sampled by bronchoalveolar lavage (BAL). Bacterial topography data revealed that the segment with sMPLC lesions provided evidence of specific colonizing bacteria in segments with lesions. After taxonomic annotation, we identified 4863 phylotypes belonging to 185 genera and 10 different phyla. The four most abundant specific bacterial community members detected in the airway containing sMPLC lesions were Clostridium, Actinobacteria, Fusobacterium, and Rothia, which all peaked at the segments with sMPLC lesions. This study begins to define the bacterial topography of the respiratory tract in patients with sMPLC and provides an approach to specimen acquisition for sMPLC, namely BAL fluid obtained from segments where lesions are located.

Analysis of the unplanned reoperation following surgical treatment of pulmonary tumor.

BACKGROUND: In this study, we aimed to summarize the extremely important lesson and experience in the whole process of surgical treatments of lung tumors for the benefit of steps taken to prevent against unplanned reoperation. METHODS: Demographical and clinical information of 7732 patients were retrospectively retrieved and reviewed, who were diagnosed with pulmonary tumor and underwent surgical treatments from January 2016 to March 2021. Those patients who underwent unplanned reoperation for the treatment of severe complications were focused carefully and analyzed meticulously. RESULTS: A total of forty-one patients (41/7732) received 44 unplanned reoperations. Among them, eight and thirty-three patients were diagnosed with benign and malignant tumor, respectively. The incidence of unplanned reoperations seemed to be similar on both sides (Left vs. Right: 12/3231 vs. 29/4501, p = 0.103). Lobectomy plus segmentectomy is prone to reoperation (2/16, 12.5%) as compared to the other types of surgery. The complications leading to reoperation was hemothorax, including active hemorrhage (23/44, 52.3%) and clotted hemothorax (6/44, 13.6%), chylothorax (8/44, 18.2%), and the others (7/44, 15.9%) including bronchopleural fistula, torsion, or injury of right middle bronchus and pulmonary bulla rupture. The morbidity and mortality after unplanned reoperation were 17.1% (7/41) and 12.2% (5/41), respectively. CONCLUSIONS: Bronchi or vessel stumps, the surgical edges of the lung parenchyma, and pleural adhesions should be checked to avoid postoperative bleeding. Prophylactic ligation of the thoracic duct should be recommended in case of the suspected oily-like exudation in the lymph node bed. Smooth expansion of the middle lobe is important to avoid narrowing and torsion before transection of the bronchus.

Circulating tumor cells with epithelial-mesenchymal transition markers as potential biomarkers for the diagnosis of lung cancer.

BACKGROUND: Circulating tumor cells (CTCs) can be clustered into three subtypes according to epithelial-mesenchymal transition (EMT) markers: CTCs with epithelial markers (E-CTCs), CTCs with mesenchymal markers (M-CTCs), and CTCs with both markers (E&M-CTCs). CTC detection has clinical implications in the diagnosis of lung cancer (LC). AIM: To clarify the diagnostic value of CTCs categorized by EMT markers in LC. METHODS: The study included 106 patients with lung adenocarcinoma, including 42 ground-glass opacities (GGO) and 64 solid lesions, who underwent surgery between July 2015 and December 2019. Eleven patients with benign tumors and seventeen healthy controls were included. CTCs in peripheral blood and associated EMT markers were detected preoperatively using the CanPatrolTM technique. The diagnostic power of CTCs for discriminating LC cases from controls was analyzed by the receiver operating characteristic (ROC) curve. The CytoploRare technique was used in 20 cases and 18 controls for validation, and Kappa values were calculated to evaluate consistency between techniques. RESULTS: Of the 106 LC cases, 94 (89.6%) had at least one CTC. CTCs were detectable in 35 (83.3%) of 42 GGO cases. Total CTCs and E&M-CTCs were significantly more frequent in LC cases than in benign or healthy controls. The proportion of M-CTCs plus E&M-CTCs increased gradually from healthy controls, to benign controls, to LC cases. The area under the ROC curve of total CTCs and E&M-CTCs was > 0.8 and > 10.75, respectively. The combined sensitivity of total-CTCs and E&M-CTCs was 85.85% for LC patients (80.95% for GGO patients) and the specificity was 78.57%. The Kappa value was 0.415, indicating relative consistency between CanPatrolTM and CytoploRare. CONCLUSION: CTC detection is valuable for distinguishing LC from controls, and particularly E&M-CTC detection warrants further study.

Is the presence of lung injury in COVID-19 an independent risk factor for secondary lung cancer?

The morbidity and mortality of lung cancer are increasing. The Corona Virus Disease 2019 (COVID-19) is caused by novel coronavirus 2019-nCoV-2, leading to subsequent pulmonary interstitial fibrosis with chronic inflammatory changes, e.g., inflammatory factors repeatedly continuously stimulating and attacking the alveolar epithelial cells. Meanwhile, 2019-nCoV-2 can activate PI3K/Akt and ERK signaling pathways, which can play the double roles as both anti-inflammatory and carcinogenic factors. Moreover, hypoxemia may be developed, resulting in the up-regulation of HIF-1 α expression, which can be involved in the occurrence, angiogenesis, invasion and metastasis of lung cancer. Additionally, the immune system in 2019-nCoV-2 infected cases can be suppressed to cause tumor immune evasion. Therefore, we speculate that COVID-19 may be a risk factor of secondary lung cancer.

Anxiety after Sympathectomy in patients with primary palmar hyperhidrosis may prolong the duration of compensatory hyperhidrosis.

BACKGROUND: Compensatory hyperhidrosis (CH) is a frequent side effect after sympathectomy for the treatment of primary palmar hyperhidrosis. We determined the effects of demographic and clinical factors which may increase the duration of CH (DCH). METHODS: One hundred twenty-two patients who had undergone sympathectomies from 2014 to 2016 were retrospectively reviewed. Anxiety was evaluated using the State and Trait Anxiety Inventory score. Follow-up evaluations continued until CH remitted. A Cox proportional hazards model was used to determine the association between DCH and variables. RESULTS: DCH ranged from 5 to 27 weeks (median, 11.47 weeks). Severe CH (HR = 0.318, 95% CI, 0.136-0.741) and exacerbated anxiety 1 month post-operatively (HR = 0.816, 95% CI, 0.746-0.893) may prolong CH. A positive correlation between post-operative anxiety and DCH was common in patients with moderate or severe CH, and in cases with forearm CH. CONCLUSIONS: Pre- and post-operative anxiety should be evaluated, and anti-anxiety treatment is offered to patients with moderate-to-severe CH to shorten the DCH.

Circulating tumor cells in early stage lung adenocarcinoma: a case series report and literature review.

PURPOSE: The study aimed to monitor circulating tumor cells (CTCs) in early stage lung adenocarcinoma patients. RESULTS: CTCs were characterized and classified to epithelial (E-) CTCs, mesenchymal (M-) CTCs and epithelial- mesenchymal (E&M-) CTCs, as per epithelial-mesenchymal transition(EMT) biomarkers. CTCs could not be found in healthy controls. However, in cohort A, CTCs were found in 17 (17/18) cases. Detection rate of E-CTCs was lower (5/18) compared with M-CTC (10/18) or E&M-CTC (14/18). Highly abundant M-CTCs were prone to being in the tumors > 2 cm. In cohorts A and B, CTCs count increased significantly in all patients with tumor progression (7/7). Higher CTCs level or change range could be found postoperatively in the patients with tumor progression, as compared with patients with disease free survival (P < 0.01). Additionally, CTCs detected by CanPatrolTM could be validated by CytoploRare or Pep@MNPs. MATERIALS AND METHODS: We included four cohorts of patients and 20 healthy controls. In cohort A, CTCs were detected by a newly established approach, i.e., CanPatrolTM, prior to anesthesia and monitored after operation longitudinally. In cohort B, CTCs were not assessed prior to operation, but were longitudinally detected after operation. For validation, we detected FOLR(+)-CTCs by using CytoploRare and EPCAM(+)-CTCs by using Pep@MNPs prior to operation, in cohorts C and D, respectively. CONCLUSION: CTCs can be detected in early stage lung adenocarcinoma, even in adenocarcinoma in situ, and CTCs detection can effectively monitor tumor progression. The distinguishing of biomarkers of highly invasive and aggressive CTCs warrants further robust study.