The promotion of non-small cell lung cancer progression by collagen and calcium binding EGF domain 1 is mediated through the regulation of ERK/JNK/P38 phosphorylation by reactive oxygen species.

Reactive oxygen species (ROS) are metabolic by-products of cells, and abnormal changes in their levels are often associated with tumor development. Our aim was to determine the role of collagen and calcium binding EGF domain 1 (CCBE1) in oxidative stress and tumorigenesis in non-small cell lung cancer cells (NSCLC). We investigated the tumorigenic potential of CCBE1 in NSCLC using in vitro and in vivo models of CCBE1 overexpression and knockdown. Immunohistochemical staining results showed that the expression of CCBE1 in cancer tissues was significantly higher than that in adjacent tissues. Cell counting Kit 8, clonal formation, wound healing, and transwell experiments showed that CCBE1 gene knockdown significantly inhibited the migration, invasion, and proliferation of NSCLC cell lines. In terms of mechanism, the silencing of CCBE1 can significantly promote the morphological abnormalities of mitochondria, significantly increase the intracellular ROS level, and promote cell apoptosis. This change of oxidative stress can affect cell proliferation, migration, and invasion by regulating the phosphorylation level of ERK/JNK/P38 MAPK. Specifically, the downregulation of CCBE1 inhibits the phosphorylation of ERK/P38 and promotes the phosphorylation of JNK in NSCLC, and this regulation can be reversed by the antioxidant NAC. In vivo experiments confirmed that downregulating CCBE1 gene could inhibit the growth of NSCLC in BALB/c nude mice. Taken together, our results confirm the tumorigenic role of CCBE1 in promoting tumor invasion and migration in NSCLC, and reveal the molecular mechanism by which CCBE1 regulates oxidative stress and the ERK/JNK/P38 MAPK pathway.

High cervical anastomosis reduces leakage-related complications after a McKeown esophagectomy.

OBJECTIVES: Anastomotic leak (AL) is one of the most serious complications after oesophageal cancer surgery. A high cervical anastomosis using a narrow gastric tube based on optimized procedures has the potential to reduce the AL after a McKeown oesophagectomy. METHODS: A narrow gastric tube was defined as 2-2.5 cm in diameter. Meanwhile, we defined a high anastomosis (HA) and a normal anastomosis (NA) based on the position of the intraoperative cervical anastomosis above or below the level of the inferior thyroid artery, respectively. A total of 533 patients who had a McKeown oesophagectomy from March 2018 to March 2023 were included in this study, including 281 patients in the NA group and 252 patients in the HA group. Potential confounding factors in baseline characteristics were balanced by propensity score matching. RESULTS: After matching, 190 patients remained in both groups. When comparing the pathological and surgical results, we found that more lymph nodes, both in total number (21.1 ± 10.0 vs 15.8 ± 7.7, P = 0.001) and thoracic part (13.5 ± 7.8 vs10.8 ± 6.1, P = 0.005), were harvested from the HA group . The pathological T and TNM stages of patients in the HA group were earlier than those in the NA group (P = 0.001). Overall postoperative complications (P = 0.001), including pulmonary infection (P = 0.001), AL (P < 0.001), leakage-related pyothorax (P < 0.001), recurrent laryngeal nerve palsy (P = 0.031) and pleural effusion (P < 0.001), were all significantly lower in the HA group. Finally, multivariable logistic regression analysis indicated that HA was an independent protective factor for AL (odds ratio = 0.331, 95% confidence interval: 0.166-0.658; P = 0.002). CONCLUSIONS: For patients undergoing a McKeown oesophagectomy, a high cervical anastomosis using a narrow gastric tube can effectively reduce leakage-related complications.

Circular RNA circATP9A promotes non-small cell lung cancer progression by interacting with HuR and by promoting extracellular vesicles-mediated macrophage M2 polarization.

BACKGROUND: CircRNA is recognized for its significant regulatory function across various cancers. However, its regulatory role in non-small cell lung cancer (NSCLC) is still largely uncharted. METHODS: Analysis based on public databases is completed using R software. circATP9A was identified by two circRNA datasets of NSCLC from the Gene Expression Omnibus database. To examine the impact of circATP9A on the phenotype of NSCLC, we conducted both in vitro and in vivo functional experiments. The mRNA and protein levels of specific molecules were determined through quantitative real-time PCR and western blot assays. RNA pulldown and RNA immunoprecipitation assays were performed to verify the interaction between RNA and protein. The functional role of extracellular vesicles (EVs)-circATP9A on tumor-associated macrophage (TAM) polarization was assessed using co-culture system and cell flow cytometry. RESULTS: Here, we elucidates the functional role of circATP9A in NSCLC. We demonstrated that circATP9A can foster the progression of NSCLC through in vivo and in vitro experiments. From a mechanistic standpoint, circATP9A can interact with the HuR protein to form an RNA-protein complex, subsequently amplifying the mRNA and protein levels of the target gene NUCKS1. Further, the PI3K/AKT/mTOR signaling was identified as the downstream pathways of circATP9A/HuR/NUCKS1 axis. More notably, hnRNPA2B1 can mediate the incorporation of circATP9A into EVs. Subsequently, these EVs containing circATP9A induce the M2 phenotype of TAMs, thereby facilitating NSCLC development. CONCLUSIONS: Our discoveries indicate that circATP9A could serve as a promising diagnostic indicator and a therapeutic target for NSCLC.

Perioperative tislelizumab plus chemotherapy for locally advanced resectable thoracic esophageal squamous cell carcinoma trial: a prospective single-arm, phase II study (PILOT trial).

BACKGROUND: The promising therapeutic outcomes of neoadjuvant immunotherapy combined with chemotherapy in the treatment of locally advanced esophageal squamous cell carcinoma (ESCC) have been confirmed by several phase II clinical trials and have been widely demonstrated in clinical work. Theoretically, postoperative adjuvant immunotherapy may further improve the therapeutic effect, but there is still lack of evidence. The aim of this study was to analyse the safety and efficacy of perioperative immunotherapy (tislelizumab) in locally advanced resectable thoracic ESCC (PILOT trial). METHODS: Seventy-three eligible patients with pathologically confirmed thoracic ESCC of clinical T1b-3N1-3M0 or T3N0M0 stage were allocated to receive neoadjuvant immunotherapy (tislelizumab 200 mg d1, q3w × 2 cycles) plus chemotherapy (nad-paclitaxel 260 mg/m2 d1 + carboplatin AUC = 5 d1, q3w × 2 cycles) treatment. Patients with pathologic complete response (pCR) after esophagectomy received adjuvant tislelizumab (200 mg every 3 weeks for up to one year), and patients with non-pCR were assigned adjuvant tislelizumab plus chemotherapy for two cycles and then maintenance tislelizumab (200 mg every 3 weeks for up to 15 cycles). The primary endpoint of this study is 2-year disease-free survival (DFS) in non-pCR patients. The secondary endpoints include pCR rate, major pathological response rate, 2-year DFS in pCR patients, R0 resection rate, adverse events, and overall survival. DISCUSSION: This protocol was reviewed and approved by the Ethics Committee of Shanghai Chest Hospital (IS23059). This is the first prospective clinical trial to investigate the safety and efficacy of perioperative immunotherapy for locally advanced resectable thoracic ESCC. We hypothesize that perioperative immunotherapy could be a promising therapeutic strategy that can provide better 2-year DFS in non-pCR patients. TRIAL REGISTRATION: ClinicalTrial.gov: NCT0605633.

The HDAC2-MTA3 interaction induces nonsmall cell lung cancer cell migration and invasion by targeting c-Myc and cyclin D1.

Genome-wide association studies have identified numerous single-nucleotide polymorphisms (SNPs) associated with lung cancer; however, the functions of histone deacetylase 2 (HDAC2) rs13213007 and HDAC2 in nonsmall cell lung cancer (NSCLC) remain unclear. Here we identified HDAC2 rs13213007 as a risk SNP and showed that HDAC2 was upregulated in both peripheral blood mononuclear cells (PBMCs) and NSCLC tissues with the rs13213007 A/A genotype compared with those with the rs13213007 G/G or G/A genotype. Patient clinical data indicated strong associations between rs13213007 genotype and N classification. Immunohistochemical staining confirmed that higher expression of HDAC2 was associated with NSCLC progression. Furthermore, we generated 293T cells with the rs13213007 A/A genotype using CRISPR (clustered regularly interspaced short palindromic repeats)/Cas9 gene editing. Chromatin immunoprecipitation sequencing followed by motif analysis showed that HDAC2 can bind to c-Myc in rs13213007 A/A 293T cells. Cell Counting Kit-8, colony formation, wound-healing, and Transwell assays revealed that HDAC2 upregulates c-Myc and cyclin D1 expression and promotes NSCLC cell proliferation, migration, and invasion. Co-immunoprecipitation, quantitative reverse transcription-polymerase chain reaction, and western blot analysis assays showed that MTA3 interacts with HDAC2, decreases HDAC2 expression, and rescues the migration and invasion abilities of NSCLC cells. Taken together, these findings identify HDAC2 as a potential therapeutic biomarker in NSCLC.

Prone position thoracoscopic-assisted total mesoesophageal excision: initial experiences and benefits of lymph node dissection.

OBJECTIVE: Total mesoesophageal excision (TME) is a promising procedure. Prone position thoracoscopic-assisted TME might be a good choice, even without robust evidence yet. Therefore, it is necessary to explore the safety and efficacy of this procedure. METHODS: We retrospectively analyzed the short-term outcomes regarding intraoperative unplanned events, postoperative complications, and lymphadenectomy in 61 patients who underwent prone position thoracoscopic-assisted TME from June, 2020 to August, 2021. The learning curve was also defined. RESULTS: Of these sixty-one patients, there were 10, 24 and 27 cases of tumor in the upper, middle, and lower thoracic, respectively. Although there were five cases of unplanned events during surgery, no conversion to thoracotomy occurred. The median thoracic operation time was 113(43-161) minutes, R0 resection rate was 93.4% (57/61), and negative circumferential resection margin rate was 96.7% (59/61). Median overall lymph node dissection was 21(9-47), with 13(5-41) thoracic lymph node dissection. Incidence of postoperative pulmonary complications, cardiovascular complications, and leakage were 9.8%, 3.3%, and 9.8%, respectively, with no death within 30 days after operation. The positive rate of middle and lower mediastinal lymph nodes was 1.1%, 3.5%, and 2.4% for upper, middle, and lower tumors, and 5.5%, 1.8%, and 1.3% for pT3-4, pT2, and pT1 patients. Learning curve showed that 36 cases are the best cut-off value for proficiency of prone position thoracoscopic-assisted TME. CONCLUSIONS: The prone position thoracoscopic-assisted TME is a safe procedure that is more conducive to thoracic lymph node dissection, especially for middle and lower mediastinum.

A Multicenter Retrospective Cohort Study on Superior Vena Cava Resection in Non-Small-Cell Lung Cancer Surgery.

BACKGROUND: Surgery for non-small-cell lung cancers (NSCLCs) invading the superior vena cava (SVC) is rarely performed due to surgical complexities and reported poor prognoses. Different methods have been described to reconstruct the SVC, such as direct suture, patch use or prosthesis, according to its circumferential involvement. The aim of our study was to analyze the short- and long-term results of different types of SVC resection and reconstruction for T4 NSCLCs. METHODS: Between January 2000 and December 2019, 80 patients received an anatomical lung resection with SVC surgery in this multicenter retrospective study. The partial resection and direct suture or patch reconstruction group included 64 patients, while the complete resection and prosthesis reconstruction group included 16 patients. The primary endpoints were as follows: long-term survival and disease-free survival. The secondary endpoints were as follows: perioperative complications and 30- and 90-day mortality. Unpaired t-tests or Mann-Whitney U tests for non-parametric variables were applied to discrete or continuous data, and the chi-square test was applied to dichotomous or categorical data. Survival rates were calculated using the Kaplan-Meier method and compared using the log-rank test. RESULTS: No differences were found between the two groups in terms of general characteristics and surgical, oncological and survival outcomes. In particular, there were no differences in terms of early (50.0% vs. 68.8%, p = 0.178) and late complication frequency (12.5% vs. 12.5%, p = 1.000), 30- and 90-day mortality, R status, recurrence, overall survival (33.89 ± 40.35 vs. 35.70 ± 51.43 months, p = 0.432) and disease-free survival (27.56 ± 40.36 vs. 31.28 ± 53.08 months, p = 0.668). The multivariate analysis demonstrated that age was the only independent predictive factor for overall survival. CONCLUSIONS: According to our results, SVC resection has good oncological and survival outcomes, regardless of the proportion of circumferential involvement and the type of reconstruction.

Characterization of the Immune Microenvironmental Landscape of Lung Squamous Cell Carcinoma with Immune Cell Infiltration.

Background: Increasing evidence supports that immune cell infiltration (ICI) patterns play a key role in the tumor progression of lung squamous cell carcinoma (LUSC). However, to date, the immune infiltration picture of LUSC has not been elucidated. Method: TCGA was used to download multiomics data from LUSC samples. At the same time, we included two datasets on lung squamous cell carcinoma, GSE17710 and GSE157010. To reveal the landscape of tumor immune microenvironment (TIME), the ESTIMATE algorithm, ssGSEA approach, and CIBERSORT analysis are used. To quantify the ICI pattern in a single tumor, consistent clustering is used to determine the LUSC subtype based on the ICI pattern, and principal component analysis (PCA) is used to obtain the ICI score. The prognostic value of the Kaplan-Meier curves is confirmed. GSEA (Gene Set Enrichment Analysis) was used to perform functional annotation. To investigate the immunotherapeutic effects of the ICI score, the immunophenotyping score (IPS) is used. Finally, analyze the mutation data with the "maftools" R package. Results: We identified four different immune infiltration patterns with different prognosis and biological characteristics in 792 LUSC samples. The identification of ICI patterns in individual tumors developed under ICI-related characteristic genes based on the ICI score helps to analyze the biological process, clinical results, immune cell infiltration, immunotherapy effects, and genetic variation. Immune failure is indicated by a high ICI score subtype marked by immunosuppression. Patients with low ICI scores have an abundance of efficient immune cells, which corresponds to the immunological activation phenotype and may have therapeutic benefits. The immunophenotypic score was used as a surrogate indicator of immunotherapy results, and samples with low ICI scores obtained significantly higher immunophenotypic scores. Finally, the relationship between the ICI score and tumor mutation burden (TMB) was proven. Conclusion: This study fully clarified the indispensable role of the ICI model in the complexity and diversity of TIME. The quantitative identification of ICI patterns in a single tumor will help draw the picture of TIME and further optimize precision immunotherapy.

Longitudinal prediction of lung nodule invasiveness by sequential modelling with common clinical computed tomography (CT) measurements: a prediction accuracy study.

Background: Accurate preoperative prediction of the invasiveness of lung nodules on computed tomography (CT) can avoid unnecessary invasive procedures and costs for low-risk patients. While previous studies approached this task using cross-sectional data, this study aimed to utilize the commonly available longitudinal data of lung nodules through sequential modelling based on long short-term memory (LSTM) networks. Methods: We retrospectively included 171 patients with lung nodules that were followed-up at least once and pathologically diagnosed with adenocarcinoma for model development. Pathological diagnosis was the gold standard for deciding lung nodule invasiveness. For each nodule, a handful of semantic features, including size intensity and interval since first discovery, were obtained from an arbitrary number of CT scans available to individual patients and used as input variables to pre-operatively predict nodule invasiveness. The LSTM-based classifier was optimized by extensive experiments and compared to logistic regression (LR) as baseline with five-fold cross-validation. Results: The best LSTM-based classifier, capable of receiving data from an arbitrary number of time points, achieved better preoperative prediction of lung nodule invasiveness [area under the curve (AUC), 0.982; accuracy, 0.924; sensitivity, 0.946; specificity, 0.881] than the best LR (AUC, 0.947; accuracy, 0.906; sensitivity, 0.938; specificity, 0.847) classifier. Conclusions: The longitudinal data of lung nodules, though unevenly spaced and varying in length, can be well modeled by the LSTM, allowing for the accurate prediction of nodule invasiveness. Given that the input variables of the sequential modelling consist of a few semantic features that are easily obtained and interpreted by clinicians, our approach is worthy further investigation for the optimal management of lung nodules.

Analysis of the prognostic role and biological characteristics of circulating tumor cell-associated white blood cell clusters in non-small cell lung cancer.

Background: Recently, circulating tumor-cell-associated white blood cell (CTC-WBC) clusters have been reported to have prognostic value in some cancers. The prognostic role of CTC-WBC clusters in lung cancer has not yet been elucidated. Very little information is available about the biological characteristics of CTC-WBC clusters. Methods: A total of 82 patients with non-small cell lung cancer (NSCLC) were included in this study, and 61 patients with advanced-stage disease were closely followed-up. All patients had blood drawn prior to treatment. Subtraction enrichment and immunostaining-fluorescence in situ hybridization (SE-iFISH) platform was used to isolate and identify CTCs and CTC-WBC clusters. Kaplan-Meier survival analysis and Cox regression analysis were applied to assess patient progression-free survival (PFS). Further, qualitative and quantitative analyses the size and ploidy characteristics of CTC-WBC clusters. Results: Firstly, CTC-WBC clusters appeared more in the advanced (stage III and IV) stage (P=0.043) than in the early stage. Furthermore, the multivariable analysis (Cox proportional hazards model) revealed that the high-CTC (≥7/6 mL) group and CTC-WBC clusters (≥1/6 mL) positive group both had significantly worse PFS, with a hazard ratio (HR) of 2.89 [95% confidence interval (CI): 1.36-6.17, P=0.006] and 2.18 (95% CI: 1.07-4.43, P=0.031), respectively. In the conjoint analysis, compared to patients with <7 CTCs/6 mL without CTC-WBC clusters, patients with ≥7 CTCs/6 mL with CTC-WBC clusters had the highest risk of progression (HR =7.13, 95% CI: 2.51-20.23, P<0.001). In addition, the presence of ≥3-cell CTC-WBC clusters in patients may indicate a shorter PFS (P<0.05) and a higher risk of progression (HR =2.90, 95% CI: 1.06-7.89, P=0.037). Furthermore, compared with the characteristics of the total CTCs, almost all of the CTCs that could recruit WBCs were large cells (≥5 µm) and exhibited polyploidy (≥ tetraploid) (both P<0.01). Conclusions: The presence of CTC-WBC clusters was an independent prognostic factor for advanced NSCLC. The joint analysis of CTCs and CTC-WBC clusters could provide additional prognostic value to the enumeration of CTCs alone. Besides, most of the CTCs in CTC-WBC clusters were large polyploid cells.

Preoperative Changes of Lung Nodule on Computed Tomography and Their Relationship With Pathological Outcomes.

Background: Whether changes of lung nodules on computed tomography could bring us helpful information related to their pathological outcomes remained unclear. Materials and Methods: This retrospective study was carried out among 1,185 cases of lung nodules in Shanghai Chest Hospital from January 2015 to April 2017, which did not shrink or disappear after preoperative follow-up over three months. Their imaging features, changes, and clinical characteristics were collected. A separate analysis was performed in nodules with or without growth in long-axis diameter after follow-up, searching significant changes related to nodule malignancy and the median interval of follow-up for reference. Further study was performed similarly in malignant nodules for discrimination of malignant grading. Results: Most nodules were stable (n = 885, 75%), whereas others grew (n = 300, 25%). For predicting nodule malignancy, increase in density (>10 Hounsfield units, median follow-up of 549 days) played an important role in growing group whereas it failed in stable group, and the increase in size was less significant in growing group. For discrimination of malignant grading, increase in density (>70 Hounsfield units, median follow-up of 366 days) showed its significance in stable group, and so did increase in size in growing group (maximum diameter growth >3.3 mm, median follow-up of 549 days, or average diameter growth >3.1 mm, median follow-up of 625 days). Conclusions: There were significant changes of lung nodules by follow-up on computed tomography, related to their pathological outcomes. The predictive power of increase in density or size varied in different situations, whereas all referred to a long-time preoperative follow-up.

Surgical results of non-small cell lung cancer involving the heart and great vessels.

BACKGROUND: The surgical treatment of advanced non-small-cell-lung-cancer (NSCLC) invading mediastinal organs and great vessels is still controversial. The aim of this multicentre study is to analyse oncological outcomes, surgical outcomes and prognostic factors of patients with NSCLC involving heart and great vessels. METHODS: 362 patients treated surgically for locally advanced T4-NCSLC between 1990 and 2020 were retrospectively reviewed. Patients were divided into five subgroups: pulmonary artery(n = 129), left atrium(n = 82), superior vena cava(n = 80), aorta(n = 43), and multiple vascular structures(n = 28). Resection was complete in 327(90%) patients. RESULTS: Overall 90-day mortality was 8.8%, influenced by poly-transfusions, pneumonectomy, bronchopleural fistula and previous cardiovascular disease (4.5HR.p = 0.03, 3.7HR p = 0.01, 14.0HR.p < 0.001 and 3.0HR p < 0.01). One-, 3- and 5-year survival rates were 75%, 43%, 33%, respectively and there were significant differences among the five groups(p < 0.001). Survival was significantly affected by induction radiotherapy, nodal status, pTNM-stage and radicality (3.8HR p = 0.03, 2.6HR p = 0.001, 1.6HR p < 0.05 and 1.6HR p < 0.05). CONCLUSIONS: Surgery provided acceptable results in selected patients with T4-NSCLC with major vascular infiltration in expert centres. Nodal-status and radicality influenced the overall-survival and disease-free survival. Neoadjuvant chemotherapy appears to have a positive effect on long-term results, particularly in N2-patients.

LRG1 in pancreatic cancer cells promotes inflammatory factor synthesis and the angiogenesis of HUVECs by activating VEGFR signaling.

Background: This study aimed to investigate the roles of leucine-rich alpha-2-glycoprotein 1 (LRG1) in regulating angiogenesis during pancreatic cancer (PC) pathogenesis. Methods: LRG1 expression in tissues was detected by qRT-PCR and immunohistochemistry. LRG1 in BxPC-3 and Capan-2 cells was knocked down or overexpressed. Cell viability and the migration and invasion abilities of cells were analyzed using the Cell Counting Kit-8 (CCK-8) assay and Transwell system, respectively. Interleukin-1 beta (IL-1ß), IL-18, and vascular endothelial growth factor A (VEGFA) contents in cell culture were measured by ELISA, and the angiogenesis of HUVECs was assessed by the in vitro tube formation assay. In vitro LRG1 expression in BxPC-3 and Capan-2 cells was determined using immunofluorescence. Results: The results showed that LRG1 expression was significantly increased in pancreatic cancer tissues and cell lines. LRG1 knockdown inhibited the viability, migration, invasion, and IL-1ß and IL-18 synthesis of BxPC-3 and Capan-2 cells. VEGFA synthesis in BxPC-3 and Capan-2 cells was also inhibited by LRG1 knockdown, which caused impaired tube formation of co-cultured HUVECs. LRG1 overexpression enhanced the viability, migration, and invasion of BxPC-3 and Capan-2 cells, also causing elevated tube formation of HUVECs and IL-1ß and IL-18 synthesis in co-cultures of HUVECs and BxPC-3 or Capan-2 cells. Silencing of VEGF receptor (VEGFR) abrogated the enhanced tube formation and IL-1ß and IL-18 synthesis in HUVECs co-cultured with BxPC-3 or Capan-2 cells overexpressing LRG1. Conclusions: In conclusion, LRG1, which is highly expressed in pancreatic cancer cells, promotes inflammatory factor synthesis and the angiogenesis of HUVECs though activating the VEGFR signaling pathway.

Long term results of surgery for NSCLC and aortic invasion. A multicenter retrospective cohort study.

BACKGROUND: Aortic invasion from non-small cell lung cancers (NSCLC) is a relative contraindication to surgery for oncological and technical reasons. Only a few studies have been published showing good results. Our aim was to evaluate short and long-term results of surgery for T4 NSCLC with aortic resection. METHODS: This is a multicenter retrospective study including 47 patients (33 males and 14 females) who received a major lung resection with aortic surgery in our centers between January 2000 and December 2016. RESULTS: Adenocarcinoma was diagnosed in 31 patients (66.0%). Induction therapy was used in 14 patients. Pneumonectomy was performed in 34 patients (72.3%). A subadventitial dissection with or without endovascular stent graft was carried out in 40 patients (85.1%), a cardiopulmonary bypass was used in 3 patients and left heart bypass in 4. Intraoperatively, two patients had bleeding (4.3%) and one ventricular fibrillation (2.1%). Twenty-three patients (48.9%) experienced at least one postoperative complication. A radical resection was achieved in 39 patients (83.0%). Thirty-day and 90-day mortality were 2.1% and 4.3%. One-, 3- and 5-year overall survival were 85.1%, 57.4% and 53.2%. Overall and disease-free survivals were significantly influenced by pathological lymph node status and R status that were independent predictive factors for poorer survival at the multivariate analyses. CONCLUSIONS: Aortic resection during surgery for NSCLC is a challenging situation. Nevertheless, oncologic outcomes may be favorable in selected cases justifying a risky procedure that should be performed in experienced hands.

Electromagnetic bronchoscopy guided microwave ablation for early stage lung cancer presenting as ground glass nodule.

BACKGROUND: Patients with early-stage lung cancer are sometimes medically inoperable, and for patients with multiple primary lung cancers, surgical resection alone sometimes proves to be impractical. Local treatments like microwave ablation (MWA) are investigational alternatives for these patients. Most reported MWA procedures for lung cancers are performed percutaneously under CT guidance. MWA navigated by electromagnetic bronchoscopy (ENB) has been limitedly studied. In this study, we aimed to evaluate the safety and feasibility of MWA under ENB guidance in patients with inoperable early-stage lung cancers or multiple primary lung cancers which cannot be completely resected. METHODS: From June 2019 to December 2020, preliminary attempts of ENB-guided MWA were made in five medically inoperable patients with a single early-stage lung cancer and ten patients with multiple primary lung cancers which were difficult to resect at the same time. For patients with concomitant pulmonary nodules which needed surgical resection, thoracoscopic resections were performed following ENB-guided MWA. The safety, feasibility, and technique effectiveness of treatments were evaluated. RESULTS: ENB-guided MWA for 15 ground glass nodules (GGNs) in 15 patients was completed in accordance with the planned protocol. Biopsy of 13 GGNs showed malignancy. Five patients received simple ENB-guided MWA without simultaneous surgical resection and ten patients received simultaneous surgical resection for 13 concomitant pulmonary nodules. CT scan by the first postoperative week showed technique effectiveness of ablation for 11 nodules indicated for MWA. Four patients had mild complications after the procedure and recovered shortly after treatment. CONCLUSIONS: For medically inoperable patients with a single GGN manifesting early-stage lung cancer and patients with multiple primary early-stage lung cancers which cannot be resected at the same time, ENB-guided MWA might be a safe and feasible alternative local treatment, whether combined with surgical resection or not. However, large, prospective, randomized, multicenter studies are needed to confirm its role in the treatment of early-stage lung cancer.

Should we distinguish between intra and extrapericardial pulmonary artery involvement in NSCLC? A multicenter retrospective case-control study.

BACKGROUND: T4 tumours comprise a heterogeneous group of locally invasive non-small cell lung cancers (NSCLC). Intrapericardial and extrapericardial involvement of the pulmonary artery (PA) may have a different prognosis. We compared the short and long-term surgery outcomes for NSCLC of the PA with intrapericardial or extrapericardial involvement. METHODS: This is a multicenter retrospective study that included 129 patients who received an anatomical resection with PA resection and reconstruction in our centres between January 2000 and December 2018. Extrapericardial group included 70 patients, while the intrapericardial included 59. RESULTS: Differences in outcomes were found in terms of left side surgery (more common in extrapericardial, p = 0.010), type of lung resection (p < 0.001), Clavien-Dindo score (p = 0.012) and 90-day mortality (1.4 vs 16.9%, p = 0.002). Overall survival (OS, 91.11 ± 63.78 vs 63.78 ± 58.241 months, p = 0.008) and tumour-free survival (TFS, 68.17 ± 71.57 vs 45.44 ± 61.32 months, p = 0.007) were statistically different. OS stratification for performed pneumonectomy, pathological lymph node status and pattern of recurrence were statistically different (p = 0.017, 0.040, <0.001). Differences were found in terms of recurrence months stratified for recurrence pattern (p < 0.001). CONCLUSIONS: According to our results, the difference between PA involvement is significant in terms of survival and complications. A T4 subset or a shift to T3 for extrapericardial involvement of the PA may lead to a change in staging and surgical approach for these patients.

Hippo Pathway Core Genes Based Prognostic Signature and Immune Infiltration Patterns in Lung Squamous Cell Carcinoma.

BACKGROUND: We investigated the prognostic effects and their patterns of immune infiltration of hippo pathway core genes in lung squamous cell carcinoma, in order to find some clues for underlying mechanisms of LUSC tumorigenesis and help developing new therapeutic methods. METHODS: The mutational data, transcriptome data and corresponding clinical medical information of LUSC patients were extracted from The Cancer Genome Atlas (TCGA) database. Differential expression genes (DEGs) and Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were explored. Survival analysis for the hippo core genes and the prognostic model were performed. Immune infiltration was estimated by CIBERSORT algorithm and some immune checkpoints-related genes were further investigated. RESULTS: Overall, 551 LUSC samples were included in our study, consisting of 502 LUSC tumor samples and 49 adjacent normal samples, respectively. There were 1910 up-regulated DEGs and 2253 down-regulated DEGs were finally identified. The top five mutational hippo pathway core genes were LATS1 (4%), WWC1 (2%), TAOK1 (2%), TAOK3 (2%), and TAOK2 (2%), respectively. the mutation of LATS2 was highly associated with co-mutational NF2 (P <0.05) and TAOK1 (P <0.05). In survival analyses, we found only WWC1 (log-rank p = 0.046, HR = 1.32, 95% CI = 1-1.73) and LATS2 (log-rank p = 0.013, HR = 1.41, 95%CI = 1.08-1.86) had significant prognostic roles. After getting the three subgroups according to the subtyping results, we demonstrated that T cell gamma delta (p = 5.78e-6), B cell memory (p = 4.61e-4) and T cell CD4+ memory resting (p = 2.65e-5) had significant differences among the three groups. SIGLEC15 (P <0.01) and CD274 (P <0.05) also had statistical differences among the three subgroups. CONCLUSIONS: Our study verified the prognostic roles of WWC1 and LATS2 in LUSC patients. Immune checkpoints-related genes SIGLEC15 and CD274 had statistical differences among the three subgroups, which may provide new perceptions on the molecular mechanisms in LUSC and maybe helpful for precisely selecting specific LUSC patients with potential immunotherapy benefits.

Preoperative peripheral blood neutrophil-to-lymphocyte ratios (NLR) and platelet-to-lymphocyte ratio (PLR) related nomograms predict the survival of patients with limited-stage small-cell lung cancer.

BACKGROUND: We aim to establish neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) related nomograms based on the clinical data and peripheral blood markers to predict the survivals of patients with limited-stage small-cell lung cancer (LS-SCLC). METHODS: A total of 299 LS-SCLC patients after surgery were enrolled in this study. Univariate and multivariate analyses were conducted to select independent prognostic factors to develop the nomograms and then subjected to bootstrap internal validation. The optimal cutoff value of NLR and PLR before surgery was calculated by X-tile (version 3.6.1) and the overall survival (OS) was analyzed by Kaplan-Meier method and compared by log-rank test. RESULTS: According to the X-tile calculation, the NLR value and PLR cutoff values are 2.6 and 156.7, respectively. The prognosis of patients with elevated NLR or PLR value was significantly worse than patients with lower NLR (HR =1.798, 95% CI: 1.284-2.518, P=0.001) or PLR (HR =1.781, 95% CI: 1.318-2.407, P<0.001) value. Two Nomograms were developed according to the two multivariate cox regression models based on NLR and PLR. Concordance index (C-index) curves and calibration curves show that the two models have a better effect in predicting prognosis. At the same time, compared with the tumor node metastasis (TNM) staging system, our models also show better accuracy and stability. CONCLUSIONS: Elevated NLR and PLR predict poor prognosis in their respective nomograms in patients with LS-SCLC.

Application of low anterior mediastinal tracheostomy for locally advanced cervicothoracic esophageal cancer undergoing total laryngopharyngoesophagectomy: a case report.

A sixty-six year-old woman came to hospital, complaining of dysphagia and weight loss. Esophagoscope showed a neoplasm between 15 and 20 cm from the incisors, biopsy revealed esophageal squamous cell carcinoma. Chest computed tomography (CT) showed that the cervical esophageal wall became thicker, the narrowing of the lumen extended downwards to the upper thoracic esophagus. Tumor invaded the membranous parts of the 5th to 12th rings of the trachea, and no swollen lymph nodes were observed in the mediastinum. The clinical stage was cT4N0M0 with borderline resectable possibility. The patient was assessed with stable disease after receiving two courses of neoadjuvant chemotherapy using DTX/CDDP/5-FU strategy. After a standard multidisciplinary treatment evaluation, total laryngopharyngoesophagectomy plus low anterior mediastinal tracheostomy (AMT) was performed. To ensure radical resection, we innovatively adopted the application of Double S-shaped myocutaneous flaps, which helps to extend the trachea and facilitate the stoma. Meanwhile, we removed the upper sternum, sternum stem, clavicle head and first and second costal cartilage to facilitate the tracheostomy and reduce the space around the stoma to avoid fluid accumulation. The pathological result showed pT4bN0M0 stage with partial response after neoadjuvant chemotherapy. This patient developed a minor anastomotic leakage which was effectively managed. Finally, she was discharged successfully 21 days after surgery.