Neoadjuvant therapy does not increase postoperative morbidity of sleeve lobectomy in locally advanced non-small cell lung cancer.

OBJECTIVES: To evaluate the feasibility and safety of sleeve lobectomy after neoadjuvant therapy by assessing the postoperative morbidity. METHODS: Patients who underwent sleeve lobectomy for non-small cell lung cancer (NSCLC) were retrospectively analyzed from January 2018 to December 2021. A total of 613 patients were enrolled, including 124 patients who received previous neoadjuvant therapy and 489 patients who did not. Propensity score matching was adopted to create a balanced cohort consisting of 97 paired cases. Patient demographics and perioperative outcomes were compared between the 2 groups, and logistic regression analysis was used to identify risk factors for postoperative complications. RESULTS: In the entire cohort, univariable logistic regression analysis showed that smoking history (odds ratio [OR], 1.501; 95% confidence interval [CI], 1.011-2.229, P = .044), open thoracotomy (OR, 1.748; 95% CI, 1.178-2.593, P = .006), and operation time more than 150 minutes (OR, 1.548; 95% CI, 1.029-2.328, P = .036) were risk factors for postoperative complications, and multivariable logistic regression analysis showed open thoracotomy was an independent risk factor (OR, 1.765; 95% CI, 1.178-2.643, P = .006). In the balanced cohort, the neoadjuvant group had a lower proportion of double-sleeve resections (3.1% vs 11.3%, P = .035) and longer postoperative chest tube drainage (6.67 ± 3.81 vs 5.13 ± 3.74 days, P < .001). However, no significant differences were observed in postoperative morbidity between the 2 groups (25.8% vs 24.7%, P = .869). The complete pathologic response of chemoimmunotherapy was significantly superior to chemotherapy alone (28.2% vs 4.1%, P < .001), and no significant differences were noted in postoperative morbidity in different neoadjuvant therapy modalities. CONCLUSIONS: After neoadjuvant therapy, sleeve lobectomy can be safely performed with no increased postoperative morbidity.

Identification of Prognostic DNA Methylation Signatures in Lung Adenocarcinoma.

Background: Increasing evidence exists of a link between DNA methylation and tumor immunotherapy. However, the impact of DNA methylation on the characteristics of the lung adenocarcinoma microenvironment and its effect on immunotherapy remain unclear. Method: This study collected TCGA-LUAD related data sets (LUAD) to explore the characteristics and regulation of 20 DNA methylation-related genes. We further identified two DNA methylation subtypes by analysing the expression profiles of these 20 DNA methylation-related genes. Subsequently, the differences in immune cell infiltration (ICI) and the expression of immune-related signaling factors among different DNA methylation subtypes were explored, and the differentially expressed genes (DEGs) among different LUAD DNA methylation subtypes were identified. Using univariate Cox to screen differentially expressed genes meaningful for survival, a DNA methylation score (DMS) was constructed based on the weight of the first and second dimensions after dimensionality reduction by principal component analysis (PCA). Our study found that DMS can better evaluate the prognosis of lung adenocarcinoma. Results: Based on DMS, LUAD samples were divided into two groups with high and low scores. The differences in clinical characteristics, tumor mutation load, and tumor immune cell infiltration between different DMS groups of LUAD were deeply explored, and the prediction ability of DMS for the benefit of immunotherapy was evaluated. Conclusions: DMS is a valuable tool for predicting survival, clinicopathological features, and immunotherapeutic efficacy, which may help to promote personalized LUAD immunotherapy in the future.

Skin-derived epithelial lining facilitates orthotopic tracheal transplantation by protecting the tracheal cartilage and inhibiting granulation hyperplasia.

Long-segment tracheal defects caused by tumours, inflammation or trauma can cause serious damage to the quality of life of patients. Although many novel neotracheas have been constructed, the therapeutic effect of orthotopic transplantation was compromised mainly because of the lack of an epithelial lining in those neotracheas. In this study, we aimed to investigate the therapeutic function of skin-derived epithelial lining for orthotopic tracheal transplantation. Strips of auricular cartilage with fixed interval were interrupted sutured on a silicone tube to mimic the cartilage rings of the native trachea. Neotrachea in the with epithelium group retained the unilateral skin as the epithelial lining in the lumen, whereas the neotrachea in the without epithelium group consisted solely of cartilage strips. After revascularized in the sternohyoid muscle, 2-cm-long tracheal defects were made and were reconstructed using these neotracheas. Our results showed that the skin-derived epithelial lining simultaneously protected the engineered tracheal cartilage and inhibited granulation hyperplasia in the tracheal lumen; further, compared with the without epithelium group, the group with epithelium showed a marked improvement in the tracheal lumen patency and the survival rate of rabbits. Our study provides a critical cue for improvements in the repair of tracheal defects via skin-derived epithelial lining and may significantly advance the clinical translation of tissue-engineered trachea.

Functional Trachea Reconstruction Using 3D-Bioprinted Native-Like Tissue Architecture Based on Designable Tissue-Specific Bioinks.

Functional segmental trachea reconstruction remains a remarkable challenge in the clinic. To date, functional trachea regeneration with alternant cartilage-fibrous tissue-mimetic structure similar to that of the native trachea relying on the three-dimensional (3D) bioprinting technology has seen very limited breakthrough. This fact is mostly due to the lack of tissue-specific bioinks suitable for both cartilage and vascularized fibrous tissue regeneration, as well as the need for firm interfacial integration between stiff and soft tissues. Here, a novel strategy is developed for 3D bioprinting of cartilage-vascularized fibrous tissue-integrated trachea (CVFIT), utilizing photocrosslinkable tissue-specific bioinks. Both cartilage- and fibrous tissue-specific bioinks created by this study provide suitable printability, favorable biocompatibility, and biomimetic microenvironments for chondrogenesis and vascularized fibrogenesis based on the multicomponent synergistic effect through the hybrid photoinitiated polymerization reaction. As such, the tubular analogs are successfully bioprinted and the ring-to-ring alternant structure is tightly integrated by the enhancement of interfacial bonding through the amidation reaction. The results from both the trachea regeneration and the in situ trachea reconstruction demonstrate the satisfactory tissue-specific regeneration along with realization of mechanical and physiological functions. This study thus illustrates the 3D-bioprinted native tissue-like trachea as a promising alternative for clinical trachea reconstruction.

Hierarchical porous bacterial cellulose scaffolds with natural biomimetic nanofibrous structure and a cartilage tissue-specific microenvironment for cartilage regeneration and repair.

The limited three-dimensional (3D) nano-scale pore structure and lack of biological function hamper the application of bacterial cellulose (BC) in cartilage tissue engineering. To address this challenge, 3D hierarchical porous BC/decellularized cartilage extracellular matrix (DCECM) scaffolds with structurally and biochemically biomimetic cartilage regeneration microenvironment were fabricated by freeze-drying technique after EDC/NHS chemical crosslinking. The BC/DCECM scaffolds exhibited excellent mechanical properties, water superabsorbency and shape-memory properties. Compared with the BC control, the BC/DCECM scaffolds exhibited enhanced cell adhesion and proliferation. Cartilage regeneration in vitro and in vivo indicated that the BC/DCECM scaffolds achieved satisfactory neocartilage tissue regeneration with superior original shape fidelity, exterior natural cartilage-like appearance and histologically cartilage-specific lacuna formation and ECM deposition. Furthermore, the BC/DCECM scaffolds achieved superior repair outcomes, as hyaline cartilage-like tissue formed within the defect sites. The present study constitutes a strong step toward the further application of BC in cartilage tissue engineering.

Comparison of minimally invasive surgery for non-flail chest rib fractures: a prospective cohort study.

BACKGROUND: To evaluate therapeutic efficacy of minimally invasive and small incision surgery [minimally invasive surgery (MIS)] in patients with non-flail chest rib fractures through a prospective cohort study. METHODS: This study included 98 patients with non-flail chest rib fractures (≥3 displaced fractures) and 66 patients undergoing MIS served as the experimental group and 32 patients receiving conservative treatment served as the matched control group. Pain index and indicators of pulmonary function [vital capacity (VC); forced expiratory volume in one second (FEV1); peak expiratory flow (PEF)] for the two groups were assessed and compared at the time of admission and before discharge. In addition, duration of pain, time required for the patient to regain the ability to perform daily self-care, mental labor, and moderate-to-severe physical labor, and duration of chest discomfort were measured during long-term follow-up and compared between the two groups. RESULTS: There were also no significant differences (P>0.05) in pain index (8 vs. 8) or indicators of pulmonary function (VC: 31.0% vs. 26.5%; FEV1: 29.9% vs. 26.7%; PEF: 15.2% vs. 12.0%) were found between the MIS and conservative treatment groups at the time of admission; while pain index (3 vs. 6), VC (42.1% vs. 35.3%), and FEV1 (44.2% vs. 35.9%) were significantly different between the two groups (P<0.05) but not in PEF (21.2% vs. 19.6%) before discharge. Long-term follow-up showed that duration of pain, time required for the patient to regain the ability to engage in daily self-care, mental labor, and moderate-to-severe physical labor, and duration of chest discomfort in the MIS group were significantly more improved than in the conservative treatment group (P<0.05). CONCLUSIONS: MIS was a simple and safe treatment that significantly relieved chest pain and rapidly restored pulmonary function and improved the long-term quality of life of patients with non-flail chest rib fractures of ≥3 ribs with displacement.

LncRNA DLEU2 accelerates the tumorigenesis and invasion of non-small cell lung cancer by sponging miR-30a-5p.

Long non-coding RNAs (lncRNAs) have been reported to participate in the pathogenesis of non-small cell lung cancer (NSCLC). However, how lncRNA deleted in lymphocytic leukaemia 2 (DLEU2) contributes to NSCLC remains undocumented. The clinical significance of lncRNA DLEU2 and miR-30a-5p expression in NSCLC was analysed by using fluorescence in situ hybridization and TCGA cohorts. Gain- and loss-of-function experiments as well as a NSCLC tumour model were executed to determine the role of lncRNA DLEU2 in NSCLC. DLEU2-sponged miR-30a-5p was verified by luciferase reporter, and RIP assays. Herein, the expression of lncRNA DLEU2 was elevated in NSCLC tissues, and its high expression or low expression of miR-30a-5p acted as an independent prognostic factor of poor survival and tumour recurrence in NSCLC. Silencing of lncRNA DLEU2 repressed the tumorigenesis and invasive potential of NSCLC, whereas re-expression of lncRNA DLEU2 showed the opposite effects. Furthermore, lncRNA DLEU2 harboured a negative correlation with miR-30a-5p expression in NSCLC tissues and acted as a sponge of miR-30a-5p, which reversed the tumour-promoting effects of lncRNA DLEU2 by targeting putative homeodomain transcription factor 2 in NSCLC. Altogether, lncRNA DLEU2 promoted the tumorigenesis and invasion of NSCLC by sponging miR-30a-5p.

Refractory Infection After Internal Fixation for Rib Fractures.

The infection of internal fixation devices of rib fractures is rare, but it is usually severe when it occurs. Existing literature indicates that removal of infected hardware is essential for the clearance of refractory infection. We report a rare case of a patient who accepted operation for rib fractures; however, his hardware infection was not controlled after the removal of internal fixation devices, until the necrotic ribs were removed by the third operation.

Necessity of thoracotomy in pulmonary metastasis of osteosarcoma.

BACKGROUND: With the popularization of minimal invasive surgery, video-assisted thoracoscopic surgery (VATS) is gradually replacing conventional thoracotomy for lung cancer and is even used for osteosarcoma patients with pulmonary metastasis. In this study, we characterized the need for open surgery by comparing computer tomography (CT) diagnosis and postoperative pathology of patients with pulmonary metastases of osteosarcoma. METHODS: A retrospective analysis was carried out on patients with underwent surgery for pulmonary metastatic osteosarcoma admitted to our hospital between January 2008 and July 2018. The numbers of pulmonary metastatic nodules suspected by preoperative CT scan were calculated in addition to the number of nodules which were resected and pathologically confirmed to be metastatic during surgery. The Spearman correlation coefficient between the number of nodules on preoperative CT scan and the number of lesions pathologically confirmed was calculated. RESULTS: In total, 69 patients undergoing 96 thoracotomy operations were included in this study. The median interval between preoperative CT examination and operation was 7 days (range, 1-44 days). The median number of the suspected nodules on preoperative CT and the pathologically positive metastases resected during operation were 1 and 3, respectively. Remarkably, 36 (37.5%) thoracotomies revealed that more metastatic nodules were detected during thoracotomy than preoperative CT scans. CONCLUSIONS: Preoperative CT examination omits a few small pulmonary metastases of osteosarcoma and there is rare progress in recent years. Therefore, we recommend that patients with pulmonary metastases of undergo thoracotomy to locate and resect all metastases as much as possible through intraoperative direct palpation.

Chest wall stabilization (CWS) in China: current situation and prospect.

Rib fracture is the most common injury in chest trauma. Chest wall stabilization (CWS) has been employed in China for 10 years and has been recognized as a safe and practical technique for rib fracture therapy. A survey entitled "Surgical Treatment for Rib Fractures" was launched at the beginning of 2018 showing that 95.6% of the hospitals surveyed performed CWS in over 30,000 cases in the past 2 years. Despite the large volume of CWS performed in China, we discovered the following characteristics: lack of large-scale clinical research, and standardized recognition of surgical indications, high costs incurred for surgical consumables, and undefined professional standard. We revealed that most of the researches on CWS in China have room for improvement. The Shanghai Sixth People's Hospital has conducted a series of CWS researches in patients with multi-rib fractures whose results showed shorter therapeutic time, pain reduction, lower morbidity, and improvement in lung function. Consequently, we formulated our own surgical indications for CWS. Thoracoscopic-assisted minimally invasive CWS surgery had been conducted in several hospitals in China. Undoubtedly, the continuous improvement of equipment and surgical techniques will inevitably lead to its further development. Researches on materials with superior absorbability or tissue compatibility have been successfully conducted in China. However, the lack of multi-center and large-sample randomized controlled trials has been one of the key factors that hampered the accurate evaluation of CWS. Accordingly, a nationwide study entitled "Evaluation of the effectiveness of surgical fixation of multiple rib fractures-a multi-center and ambispective cohort study" was initiated in June 2018. It is believed that the result of this research would considerably improve and enrich the clinical evidence on CWS in rib fracture patients.

Simultaneous Surgical Treatment of Sternum and Costal Cartilage Fractures.

Studies have confirmed that, for severe flail chest or sternal fractures and even multiple rib fractures, surgical treatment can effectively reduce hospital stay and relieve chest wall pain. However, fixation of multiple costal cartilage fractures in such a small area is a challenge if an internal fixator is simply placed directly on the sternum. This case report shares a method of simultaneous fixation of multiple costal cartilage and sternal fractures through a small incision, and it is also appropriate for multiple costal cartilage fractures without sternal fracture.

Reconstruction of anterior chest wall: a clinical analysis.

OBJECTIVE: To investigate the methods and clinical efficacy of reconstruction of chest defects with titanium sternal fixation system after the surgical resection of sternal tumors. METHODS: A total of 6 patients with sternal tumor who were diagnosed and underwent resection and repair of the chest wall defects by titanium plates system, from 2017.3 to 2017.11 in our hospital were reviewed. Their pathological types, surgical reconstruction methods, follow-up results were analyzed. RESULTS: Six cases of sternal tumor were completely resected and the sternums were reconstructed with titanium sternal fixation system. There was no operative death, postoperative chest wall deformity, abnormal breathing or complications of respiratory circulation. After 3 to 10 months of follow-up, there was no loose screw or plate exposure. Not only the thoracic appearances were good, but patients' satisfaction was high. CONCLUSIONS: Surgical resection is the best treatment for sternal tumors, no matter it is benign or malignant. Titanium sternal fixation system combine with other soft materials can reconstruct the chest wall well after resection, and this technique is efficient as well as easy to learn.