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.

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.

Comparative short-term outcomes of robotic-assisted surgery for older patients with non-small cell lung cancer: a propensity matched study.

To investigate comparative short-term outcomes of robotic-assisted surgery (RAS) versus video-assisted thoracoscopic surgery (VATS) for older non-small cell lung cancer (NSCLC) patients. Patients ≥ 65 years old with stage I-III NSCLC operated with RAS or VATS from 2016 to 2018 were consecutively included. Propensity score-matched (PSM) method was implemented to balance inter-group biases. Totally 376 participants (224 with VATS and 152 with RAS) were included. After PSM, a cohort (144 with VATS and 107 with RAS) was generated with balanced baseline characteristics. RAS was significantly superior over VATS in the majority of perioperative outcomes, such as operating time (120.8 vs. 165.1 min), conversion rate (0.0% vs. 19.4%), and length of stay (8.6 vs. 10.8 days). RAS versus VATS was significantly associated with comparable rates of postoperative complications (OR 0.642, 95% CI 0.311-1.327), except the rate of pneumonia (OR 0.161, 95% CI 0.048-0.544). RAS leads to analogous postoperative complications and seemingly accelerates the recovery time of older NSCLC patients compared with VATS.

BCAR1 plays critical roles in the formation and immunoevasion of invasive circulating tumor cells in lung adenocarcinoma.

Background: We investigated the roles of breast cancer anti-estrogen resistance 1 (BCAR1/p130Cas) in the formation and immunoevasion of invasive circulating tumor cells (CTCs) in lung adenocarcinoma (LUAD). Methods: Biomarkers of CTCs including BCAR1 and CD274, were evaluated by the CanPatrol method. Proteomics analysis of LUAD cells and exosomes after BCAR1 overexpression (BCAR1-OE) was performed by mass spectrometry. Cell functions and relevant signaling pathways were investigated after BCAR1 knockdown (BCAR1-KO) or BCAR1-OE in LUAD cells. Lastly, in vitro and in vivo experiments were performed to confirm the roles of BCAR1 in the formation and immunoevasion of CTCs. Results: High expression of BCAR1 by CTCs correlated with CD274 expression and epithelial-to-mesenchymal transition (EMT). RAC1, together with BCAR1, was found to play an important role in the carcinogenesis of LUAD. RAC1 functioned with BCAR1 to induce EMT and to enhance cell proliferation, colony formation, cell invasion and migration, and anoikis resistance in LUAD cells. BCAR1 up-regulated CD274 expression probably by shuttling the short isoform of BRD4 (BRD4-S) into the nucleus. CTCs, as well as tumor formation, were prohibited in nude mice xenografted with BCAR1-KO cells. The co-expression of BCAR1/RAC1 and BCAR1/CD274 was confirmed in LUAD. BCAR1 expression in LUAD is an indicator of poor prognosis, and it associates with immunoevasion. Conclusion: BCAR1, as a new target for the treatment of LUAD, plays roles in the formation and immunoevasion of invasive CTCs. The mechanism includes triggering EMT via RAC1 signaling and up-regulating CD274 expression by shuttling BRD4-S into the nucleus.

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.

GRP75-mediated upregulation of HMGA1 stimulates stage I lung adenocarcinoma progression by activating JNK/c-JUN signaling.

BACKGROUND: Recurrence is a major challenge in early-stage lung adenocarcinoma (LUAD) treatment. Here, we investigated the role and mechanism of high-mobility group AT-hook 1 (HMGA1) and glucose-regulated protein 75-kDa (GRP75) in stage I LUAD and evaluated their potential as biomarkers for predicting the recurrence and prognosis of stage I LUAD. METHODS: The TCGA dataset was used to investigate the clinical significance of HMGA1 and GRP75 in early-stage LUAD. The biological functions of HMGA1 and GRP75 in LUAD were investigated both in vitro and in vivo through overexpression and knockdown experiments. The interaction and regulation between HMGA1 and GRP75 were evaluated with coimmunoprecipitation and ubiquitination assays. The downstream signaling pathway of the GRP75/HMGA1 axis was investigated by mRNA-sequencing analysis. RESULTS: Both HMGA1 expression levels and GRP75 expression levels were associated with recurrence in stage I LUAD patients. In particular, HMGA1 had potential as an independent prognostic factor in stage I LUAD patients. Overexpression of GRP75 or HMGA1 significantly stimulated LUAD cell growth and metastasis, while silencing GRP75 or HMGA1 inhibited LUAD cell growth and metastasis in vitro and in vivo. Importantly, GRP75 inhibited ubiquitination-mediated HMGA1 degradation by directly binding to HMGA1, thereby causes HMGA1 upregulation in LUAD. In addition, the GRP75/HMGA1 axis played its role by activating JNK/c-JUN signaling in LUAD. CONCLUSIONS: The activation of GRP75/HMGA1/JNK/c-JUN signaling is an important mechanism that promotes the progression of stage I LUAD, and a high level of HMGA1 is a novel biomarker for predicting recurrence and a poor prognosis in stage I LUAD patients.

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.