Predicting therapeutic response to neoadjuvant immunotherapy based on an integration model in resectable stage IIIA (N2) non-small cell lung cancer.

OBJECTIVE: Accurately predicting response during neoadjuvant chemoimmunotherapy for resectable non-small cell lung cancer (NSCLC) remains clinically challenging. In this study, we investigate the effectiveness of blood-based tumor mutational burden (bTMB) and a deep learning (DL) model in predicting major pathologic response (MPR) and survival from a phase II trial. METHODS: Blood samples were prospectively collected from 45 stage IIIA (N2) NSCLC patients undergoing neoadjuvant chemoimmunotherapy. An integrated model, combining the CT-based DL score, bTMB, and clinical factors, was developed to predict tumor response to neoadjuvant chemoimmunotherapy. RESULTS: At baseline, bTMB were detected in 77.8% (35 of 45) of patients. Baseline bTMB ≥11 Muts/Mb was associated with significantly higher MPR rates (77.8% vs. 38.5%, p = 0.042), and longer disease-free survival (DFS, p = 0.043), but not overall survival (p = 0.131), compared to bTMB < 11 Muts/Mb in 35 patients with bTMB available. The developed DL model achieved an area under the curve (AUC) of 0.703 in all patients. Importantly, the predictive performance of the integrated model improved to an AUC of 0.820 when combining the DL score with bTMB and clinical factors. Baseline circulating tumor DNA (ctDNA) status was not associated with pathological response and survival. Compared to ctDNA residual, ctDNA clearance before surgery was associated with significantly higher MPR rates (88.2% vs. 11.1%, p < 0.001) and improved DFS (p = 0.010). CONCLUSIONS: The integrated model shows promise as a predictor of tumor response to neoadjuvant chemoimmunotherapy. Serial ctDNA dynamics provide a reliable tool for monitoring tumor response.

Limited resection is comparable to lobectomy for tumor size ≤ 2 cm pulmonary invasive mucinous adenocarcinoma.

OBJECTIVES: Invasive mucinous adenocarcinoma (IMA) has a rare incidence with better prognosis than nonmucinous adenocarcinoma. We aimed to investigate the prognosis between limited resection and lobectomy for patients with clinical stage IA IMA ≤ 2 cm. METHODS: Data were taken from two cohorts: In Shanghai Pulmonary Hospital (SPH) corhort, we identified 403 patients with clinical stage IA IMA who underwent surgery. In the SEER corhort, 480 patients with stage T1 IMA who after surgery were included. Recurrence-free survival (RFS) for SPH corhort, lung cancer-specific survival (LCSS) for the SEER corhort and overall survival (OS) for both corhort were compared between patients undergoing lobectomy and limited resection by Log-rank and Cox proportional hazard regression model. RESULTS: In SPH corhort, patients who underwent limited resection had equivalent prognosis than those underwent lobectomy (5-year RFS: 79.3% versus. 82.6%, p = 0.116; 5-year OS: 86.2% versus. 88.3%, p = 0.235). However, patients with IMA > 2 to 3 cm had worse prognosis than those with IMA ≤ 2 cm (5-year RFS: 73.7% versus. 86.1%, p = 0.007). In the analysis of IMA > 2 to 3 cm subgroup, multivariate analysis showed that limited resection was an independent risk factor of RFS (hazard ratio, 2.417; 95% confidence interval, 1.157-5.049; p = 0.019), while OS (p = 0.122) was not significantly different between two groups. For IMA ≤ 2 cm, limited resection was not a risk factor of RFS (p = 0. 953) and OS (p = 0.552). In the SEER corhort, IMA ≤ 2 cm subgroup, limited resection was equivalent prognosis in LCSS (p = 0.703) and OS (p = 0.830). CONCLUSIONS: Limited resection could be a potential surgical option which comparable to lobectomy in patients with clinical stage IA IMA ≤ 2 cm.

Modulating Cholesterol Metabolism via ACAT1 Knockdown Enhances Anti-B-Cell Lymphoma Activities of CD19-Specific Chimeric Antigen Receptor T Cells by Improving the Cell Activation and Proliferation.

CD19-specific CAR-T immunotherapy has been extensively studied for the treatment of B-cell lymphoma. Recently, cholesterol metabolism has emerged as a modulator of T lymphocyte function and can be exploited in immunotherapy to increase the efficacy of CAR-based systems. Acetyl-CoA acetyltransferase 1 (ACAT1) is the major cholesterol esterification enzyme. ACAT1 inhibitors previously shown to modulate cardiovascular diseases are now being implicated in immunotherapy. In the present study, we achieved knockdown of ACAT1 in T cells via RNA interference technology by inserting ACAT1-shRNA into anti-CD19-CAR-T cells. Knockdown of ACAT1 led to an increased cytotoxic capacity of the anti-CD19-CAR-T cells. In addition, more CD69, IFN-γ, and GzmB were expressed in the anti-CD19-CAR-T cells. Cell proliferation was also enhanced in both antigen-independent and antigen-dependent manners. Degranulation was also improved as evidenced by an increased level of CD107a. Moreover, the knockdown of ACAT1 led to better anti-tumor efficacy of anti-CD19 CAR-T cells in the B-cell lymphoma mice model. Our study demonstrates novel CAR-T cells containing ACAT1 shRNA with improved efficacy compared to conventional anti-CD19-CAR-T cells in vitro and in vivo.

Survival comparison of pulmonary neuroendocrine carcinoma, adenocarcinoma with neuroendocrine differentiation, and adenocarcinoma.

Background: Pulmonary adenocarcinoma with neuroendocrine differentiation (ADE_ned) is a relatively uncommon pathological classification, and there exists considerable debate regarding its prognosis and treatment. The purpose of this study was to analyze the survival difference between patients with neuroendocrine carcinoma (NEC), adenocarcinoma (ADE), or ADE_ned and to investigate the prognostic factors influencing the outcomes of individuals diagnosed with pulmonary ADE_ned. Methods: We retrieved information on 316 cases of ADE_ned, 188,823 cases of ADE, and 71,154 cases of NEC diagnosed between 2004 and 2015 from the Surveillance, Epidemiology, and End Results (SEER) database. To account for potential confounding variables, propensity score matching (PSM) was employed. Comparative analyses were conducted to estimate the overall survival (OS) and cancer-specific survival (CSS). Finally, the Cox regression models were used to identify prognostic factors associated with pulmonary ADE_ned. Results: Prior to PSM, patients with lung ADE_ned had a worse OS rate than did those with lung ADE or NEC (5-year OS rate: 13.3% vs. 26.6% vs. 15.6%; P<0.001 and P=0.009, respectively). In terms of CSS, the 5-year CSS rate of patients with ADE_ned was superior to that of NEC but inferior to that of ADE (28.7% vs. 26.8% vs. 43.8%; P=0.006 and P<0.001, respectively). Following PSM, the 5-year survival rate of patients with ADE_ned remained lower than that of individuals with ADE or NEC in terms of OS (13.3% vs. 24.4% vs. 23.0%; P<0.001 and P<0001, respectively) and CSS (28.8% vs. 58.6% vs. 43.1%; P<0.001 and P=0.006, respectively). Finally, the results of the competitive risk regression analysis demonstrated that several variables, including sex, T stage, N stage, M stage, and surgery, were found to be independent prognostic factors for patients diagnosed with pulmonary ADE_ned (all P values <0.05). Conclusions: Patients with lung ADE_ned had a significantly poorer survival outcome compared to those with lung ADE or NEC. Furthermore, sex, tumor-node-metastasis (TNM) stage, and surgery were found to be independent prognostic indicators for cases with lung ADE_ned.

Cell number regulator 8 from Salix linearistipularis enhances cadmium tolerance in poplar by reducing cadmium uptake and accumulation.

Trace metals have relatively high density and high toxicity at low concentrations. Willow (Salix genus) is an excellent phytoremediation species for soil contaminated by trace metal ions. This study identified a cell number regulator (CNR) gene family member in Salix linearistipularis exhibiting strong metal ion resistance: SlCNR8. SlCNR8 expression was affected by various metal ions, including cadmium (Cd), zinc (Zn), copper (Cu), iron (Fe), and manganese (Mn). SlCNR8 overexpression enhanced Cd, Zn, Cu, and Fe resistance in transgenic poplar seedlings (84K) compared with the wild-type (WT). Moreover, transgenic poplar seedlings showed lower root Cd uptake and less Cd accumulation than WT under Cd stress. SlCNR8 was primarily localized to the nucleus and the plasma membrane-like cell periphery. Furthermore, SlCNR8 had transcriptional activation activity in yeast. The transcript levels of multiple metal ion transporters were altered in the roots of transgenic poplar seedlings compared to WT roots under Cd stress. These results suggest that SlCNR8 may enhance Cd resistance in transgenic poplar by reducing Cd uptake and accumulation. This may be related to altered transcription levels of other transporters or to itself. Our study suggests that SlCNR8 can be used as a candidate gene for genetic improvement of phytostabilisation of trace metals by genetic engineering.

Perioperative outcomes comparison of robotic and video-assisted thoracoscopic thymectomy for thymic epithelial tumor: a single-center experience.

BACKGROUND: The advent of robot-assisted thoracoscopic surgery (RATS) has completely revolutionized the modality of thymectomy, which could reportedly achieve equivalent efficacy compared with a minimally invasive approach. This study was conducted to further compare the perioperative outcomes between these two modalities. METHODS: A retrospective single-center study that included patients receiving either a robotic or video-assisted thoracoscopic (VAT) thymectomy between February 2021 and January 2023 was conducted. All the patients were pathologically confirmed with thymic epithelial tumors. Clinical and pathological characteristics and perioperative outcomes were collected and compared between these two cohorts. RESULTS: A total of 190 patients were included in this study, with 61 (32.1%) and 129 (67.9%) receiving robotic and video-assisted thymectomy, respectively. The clinicopathological characteristics were not significantly different between these 2 groups. The size of the resected specimens in the RATS cohort was larger than the VATS cohort [median (IQR), 13.0 (8.0-16.0) vs. 9.0 (6.7-12.0) cm, p < 0.001], while the procedural duration was longer for the RATS group than its counterpart [median (IQR), 105 (85-143) vs. 85 (69-115) min, p = 0.001]. Moreover, no other significant difference was observed between these two groups. Since more than half of the robotic thymectomy was performed using a subxiphoid approach, a subgroup analysis was further conducted. Similarly, the robotic group through a subxiphoid approach harbored a longer procedural duration, and the size of the specimens obtained was larger than the VATS group [median (IQR), 14.0 (11.0-16.5) vs. 12.5 (8.5-15.0) cm, p = 0.061]. CONCLUSIONS: The early clinical efficacy of robotic thymectomy was proven comparable to the established VATS approach, and such a modality might have strength when obtaining larger specimens, which could contribute to improving long-term efficacy. Despite the longer procedural duration recorded in the early stage of conducting robotic thymectomy, further accumulation would help decrease the time.

The number of metastatic lymph nodes is more predictive of prognosis than location-based N stage for nonsmall cell lung cancer: a retrospective cohort study.

BACKGROUND: The eighth edition of nodal classification is defined only by the anatomical location of metastatic lymph nodes and has limited prognostic discrimination power. The authors aimed to evaluate the prognostic significance and discriminatory capability of the number of metastatic lymph nodes (nN) in resected nonsmall cell lung cancer. MATERIALS AND METHODS: Patients with stage IA to IIIB resected nonsmall cell lung cancer between 1 January 2009 and 31 December 2013 were analyzed as a Chinese cohort. The optimal thresholds for the nN classification were determined by the X-tile. The receiver operating characteristic curve, net reclassification improvement and standardized net benefit calculated by decision curve analysis was estimated to quantify the nN classification's performance in prognostic stratification. External validation in the surveillance, epidemiology, and end results database was performed to test the robustness of the nN classification. RESULTS: Both cohorts showed a stepwise prognosis deterioration with increasing nN. One to three, four to six, and more than six were selected as optimal thresholds of nN classification in the Chinese cohort, which included 4432 patients, then validated in the SEER cohort ( n =28 022 patients). Multivariate Cox analysis showed the nN classification was an independent predictive factor for overall survival in both cohorts (Chinese cohort and SEER cohort: N 0 vs. N 1-3 , P <0.001; N 0 vs. N 3-6 , P <0.001; N 0 vs. N >6 , P <0.001). And prognostic discriminatory capability was improved in the nN classification compared with location-based N classification [5-year NRI score, 0.106 (95% CI: 0.049-0.132) and 5-year time-independent AUC, 0.593 (95% CI: 0.560-0.625) vs. 0.554 (95% CI: 0.520-0.588), P <0.001]. CONCLUSIONS: The nN classification tended to be a superior prognostic indicator than the location-based N classification. The number of metastatic lymph nodes should be considered in the future revision of the TNM system.

Subcellular Expression Patterns of FKBP Prolyl Isomerase 10 (FKBP10) in Colorectal Cancer and Its Clinical Significance.

FKBP10, a member of the FK506-binding protein (FKBP) family, has been implicated in cancer development, although its prognostic function remains controversial. In this study, we analyzed the expression of FKBP10 in tumor tissues using online databases (TCGA) as well as our CRC cohort, and investigated the relationship between its subcellular expression pattern and patient outcomes. Cox regression analysis was used to determine the associations between different subcellular expression patterns of FKBP10 and clinical features of patients. We also discussed the expression level of FKBP10 based on different subcellular expression patterns. Our results showed that FKBP10 was significantly elevated in CRC tissues and exhibited three different subcellular expression patterns which were defined as 'FKBP10-C' (concentrated), 'FKBP10-T' (transitional) and 'FKBP10-D' (dispersive). The FKBP10-D expression pattern was only found in tumor tissues and was associated with unfavorable disease-free survival in CRC patients. High expression levels of FKBP10-C predicted an unfavorable prognosis of recurrence of CRC, while FKBP10-D did not. Our findings suggest that the subcellular expression patterns and expression level of FKBP10 play crucial prognostic roles in CRC, which revealed that FKBP10 may be a viable prognostic and therapeutic target for the diagnosis and treatment of CRC.

The additional radiotherapy to adjuvant chemotherapy improves the prognosis of stage III-N2 with highest mediastinal lymph node metastasis in non-small cell lung cancer.

INTRODUCTION: The benefits of adjuvant chemoradiation therapy (CRT) for heterogeneous pathological N2 (pN2) diseases remain unclear in non-small cell lung cancer (NSCLC). This study aimed to investigate suitable pN2 patients for adjuvant CRT. MATERIAL AND METHODS: This study retrospectively reviewed the data of patients with pN2 NSCLC in Shanghai Pulmonary Hospital from January 2012 to December 2016. Included cases were subdivided as highest mediastinal lymph node (HM) (n = 732) metastasis and non-HM metastasis (n = 677) groups according to the International Association for the Study of Lung Cancer (IASLC). Furthermore, the Kaplan-Meier and Cox models were used to evaluate the prognostic benefits of adjuvant CRT in heterogeneous pN2 subgroups. RESULTS: A total of 1409 patients were enrolled in this study, with a median follow-up time of 63.8 months. Patients with HM involvement had worse prognoses (p < 0.001 for recurrence-free survival (RFS) and overall survival (OS)). Furthermore, the survival improvement of adjuvant CRT was significant for these patients (p < 0.001 for RFS and p = 0.032 for OS), regardless of whether it was single (p < 0.001 for RFS and p = 0.029 for OS) or multiple pN2 (p < 0.001 for RFS and p = 0.026 for OS) diseases. According to multivariable cox analysis, the long-term RFS and OS in the cancerous HM group were independently predicted by pathological N stage (p = 0.002 for RFS and p < 0.001 for OS) and adjuvant CRT (p < 0.001 for RFS and p = 0.011 for OS). CONCLUSION: Metastatic HM was associated with a worse prognosis in pN2 disease. Our analysis supported that adjuvant CRT significantly improved both RFS and OS for these patients.

Inhibition of BRD4 enhanced the tumor suppression effect of dasatinib in gastric cancer.

BRD4, a member of the bromodomain and extraterminal (BET) family, is elevated in multiple cancer tissues, including gastric cancer (GC). Targeted therapy with BRD4 may help improve the overall survival of patients with GC. Meanwhile, the approved multi-target kinase inhibitor, dasatinib, was recently reported to show varied tumor-suppressive effects in GC cells. This study investigated BRD4 expression in vivo and in vitro using immunohistochemistry and western blotting, respectively. We discussed the relationship between BRD4 expression and patient prognosis. Next, the antitumor efficacy of dasatinib was measured in BRD4-knockdown GC cells to determine the role of BRD4 blockage in dasatinib treatment. Finally, molibresib, a BET inhibitor, was used to measure the cooperative function of BRD4 inhibition and dasatinib treatment in three GC cell lines. Epithelial BRD4 expression was higher in tumoral and metastatic tissues and was strongly associated with unfavorable tumor, node, and metastasis stages and survival. BRD4 expression was heterogeneous in the three GC cell lines tested in vitro. In SGC7901, a BRD4-high GC cell line, knockdown of BRD4 using specific siRNAs suppressed cell growth individually and cooperatively with dasatinib. Moreover, molibresib and dasatinib showed a cooperative effect in suppressing the proliferation of BRD4-high GC cells. In conclusion, we confirmed that increased epithelial BRD4 expression is associated with poor disease stage and prognosis in GC and BRD4 blockage might be a valuable strategy to improve the sensitivity of dasatinib and other drugs in the chemotherapy of advanced GC.

Plant cadmium resistance 6 from Salix linearistipularis (SlPCR6) affects cadmium and copper uptake in roots of transgenic Populus.

Phytoextraction in phytoremediation is one of the environmentally friendly methods used for restoring soils contaminated by heavy metals (HMs). The screening and identification of HM-resistant plants and their regulatory genes associated with HM ion transport are the key research aims in this field. In this study, a plant cadmium (Cd) resistance (PCR) gene family member, SlPCR6, was identified in roots of Salix linearistipularis, which exhibits strong HM resistance. The results revealed that SlPCR6 expression was induced in S. linearistipularis roots in response to Cd stress. Furthermore, SlPCR6 was mainly localized on the plasma membrane. Compared with the wild type, SlPCR6 overexpression reduced the Cd and copper (Cu) contents in the transgenic poplar (84 K) and increased its Cd and Cu resistance. The roots of transgenic poplar seedlings had lower net Cd and Cu uptake rates than wild type roots. Further investigation revealed that the transcript levels of multiple HM ion transporters were not significantly different between the roots of the wild type and those of the transgenic poplar. These results suggest that SlPCR6 is directly involved in Cd and Cu transport in S. linearistipularis roots. Therefore, SlPCR6 can serve as a candidate gene to improve the phytoextraction of the HMs Cd and Cu through genetic engineering.

SHP2 inhibition improves celastrol-induced growth suppression of colorectal cancer.

This study aimed to explore novel targets for celastrol sensitization in colorectal cancer (CRC) based on differentially regulated signals in response to high- or low-dose celastrol. Targeting signals were investigated using Western blotting or phosphorylated receptor tyrosine kinase (RTK) arrays. Corresponding inhibitors for the signals were individually combined with low-dose celastrol for the assessment of combined anti-CRC effects, based on proliferation, apoptosis, colony assays, and xenograft models. The potential mechanism for the combination of celastrol and SHP2 inhibition was further examined. Low-dose celastrol (<1 µM) did not effectively suppress AKT and ERK signals in CRC cells compared to high-dose celastrol (>1 µM). However, when combined with an AKT or ERK inhibitor, low-dose celastrol could cooperatively suppress CRC proliferation. Furthermore, failed AKT or ERK inhibition by low-dose celastrol may be due to reactivated RTK-SHP2 signaling with negative feedback. The combination of celastrol and the SHP2 inhibitor resulted in greatly reduced AKT and ERK signals, as well as greater inhibition of CRC growth than celastrol alone. Moreover, the mechanism underlying combination suppression was also involved in the activation of immune cell infiltration (mainly for CD8+ cells) in CRC tissues. Failure to inhibit RTK-SHP2-AKT/ERK signaling contributed to the lack of CRC growth suppression by low-dose celastrol. However, the combination of celastrol and the SHP2 inhibitor resulted in synergistic inhibition of CRC growth and provided a promising therapeutic target.

The Nursing Effect of PRECEDE Management on Occupational Exposure to Surgical Smoke: Based on a Randomized Controlled Study.

Background: Occupational exposure seriously threatens the physical and mental health of professionals and has become an important public health problem. In clinical medical and nursing work, medical staff, especially nursing staff, are faced with the status quo of occupational exposure with high risk, serious harm, and severe situation. Therefore, a sound management system must be established to control the occupational exposure of nurses. Aims: According to the PRECEDE management model, evaluate the operating room nurses' knowledge, belief, and behavior scores on the protection of surgical smoke, understand their awareness of surgical smoke and the current status of protection, improve the mastery rate and protection compliance of surgical smoke-related knowledge in the operating room, reduce the harm of surgical smoke to the human body, and provide a basis for smoke protection.Materials and methods. 125 doctors working in the operating room of our hospital were selected as the control group of this study, and 112 nonsmoke-exposed nurses working in the operating room of our hospital were selected as the observation group. The nurses' knowledge-belief behavior scores and self-evaluation scores of smoke influence were counted before and after the intervention in the operating room. SPSS25.0 was used to process the data. Tests and repeated measures analysis of variance were used to compare the effects before and after intervention. Results: After one month of intervention, the knowledge scores of nurses in the operating room on the protection of surgical smoke increased significantly, and the difference was significant (P < 0.05); the scores of related concepts, physical properties, chemical properties, and authoritative protection standards increased significantly (P < 0.05). There was no significant increase in the scores of smoke hazards (P > 0.05); the attitude of smoke protection increased significantly, which was statistically significant (P < 0.05); and the behavior compliance of smoke protection was significantly increased, which was statistically significant (P < 0.05). After one month of intervention, the self-evaluation score of smoke effect of operating room nurses decreased significantly, and the difference was statistically significant (P < 0.05). The data was analyzed by repeated measure analysis of variance. The knowledge of surgical smoke (F = 65.570, P < 0.001), attitude (F = 78.307, P < 0.001), and behavior (F = 403.015, P < 0.001) scores gradually increased. The observation group's total cholesterol, low-density lipoprotein cholesterol, and the proportion of low-density lipoprotein cholesterol were higher than that of the control group, and the proportion of high-density lipoprotein cholesterol was lower than that of the control group. The difference was statistically significant P < 0.05. Conclusion: After the intervention of operating room nurses under the guidance of PRECEDE management mode, the theoretical knowledge of operating room nurses is effectively improved, the operations are standardized, the self-evaluation scores of smoke influence are reduced, and the safety level of operating room is improved. More importantly, the health of nursing staff is fully guaranteed.

CDK inhibitor Palbociclib targets STING to alleviate autoinflammation.

Aberrant activation of stimulator of interferon genes (STING) is tightly associated with multiple types of disease, including cancer, infection, and autoimmune diseases. However, the development of STING modulators for the therapy of STING-related diseases is still an unmet clinical need. We employed a high-throughput screening approach based on the interaction of small-molecule chemical compounds with recombinant STING protein to identify functional STING modulators. Intriguingly, the cyclin-dependent protein kinase (CDK) inhibitor Palbociclib was found to directly bind STING and inhibit its activation in both mouse and human cells. Mechanistically, Palbociclib targets Y167 of STING to block its dimerization, its binding with cyclic dinucleotides, and its trafficking. Importantly, Palbociclib alleviates autoimmune disease features induced by dextran sulphate sodium or genetic ablation of three prime repair exonuclease 1 (Trex1) in mice in a STING-dependent manner. Our work identifies Palbociclib as a novel pharmacological inhibitor of STING that abrogates its homodimerization and provides a basis for the fast repurposing of this Food and Drug Administration-approved drug for the therapy of autoinflammatory diseases.

Feasibility of double sleeve lobectomy after neoadjuvant chemotherapy in patients with non-small-cell lung cancer.

OBJECTIVES: This study intends to appraise the feasibility of double sleeve lobectomy after neoadjuvant chemotherapy in central non-small-cell lung cancer with bronchovascular aggression. METHODS: This retrospective study included non-small-cell lung cancer patients who received double sleeve lobectomy from January 2014 to June 2020. Patients were divided into 2 groups: the neoadjuvant chemotherapy group and the non-neoadjuvant chemotherapy group. Demographic data and perioperative outcomes were compared between these 2 groups. RESULTS: Of the 110 patients who received double sleeve lobectomy during this period, 35 patients (31.8%) received neoadjuvant chemotherapy. Compared with the non-neoadjuvant chemotherapy group, patients who received neoadjuvant chemotherapy were associated with younger age (P = 0.026), smaller pathologic tumour size (P = 0.005), higher forced expiratory volume in 1 s (P = 0.007), higher forced expiratory volume in 1 s of predicted value (P = 0.005) and higher clinical stage (P < 0.001). In the neoadjuvant chemotherapy group, 18 patients (51.4%) attained a partial response and 17 patients (48.6%) achieved stable disease. The postoperative hospital stays (P = 0.042) and chest tube drainage duration (P = 0.030) were longer in the neoadjuvant chemotherapy group and other perioperative performances were similar between these 2 groups. No statistically significant difference was reported in postoperative complications and mortality between these 2 groups. CONCLUSIONS: The intraoperative performance and postoperative outcomes of double sleeve lobectomy following neoadjuvant chemotherapy were similar to direct surgery, indicating that double sleeve lobectomy after neoadjuvant chemotherapy is feasible and safe in central lung cancer involving both the pulmonary artery and bronchus.

Identification of filigree pattern increases the diagnostic accuracy of micropapillary pattern on frozen section for lung adenocarcinoma.

AIMS: The presence of micropapillary (MIP) in early-stage lung adenocarcinoma is associated with a poorer prognosis, especially in patients undergoing sublobectomy. However, data on the sensitivity of frozen section (FS) evaluation of MIP is still limited. We included the concept of a filigree pattern on FS to assess its effect on the diagnostic sensitivity and specificity of MIP, and to verify its prognostic value in stage T1 lung adenocarcinoma. METHODS: A panel of five pathologists evaluated 125 patients with T1 lung adenocarcinoma from January to February 2014 as a study cohort, and 151 patients from January to February 2020 as a validation cohort. The diagnostic accuracy of the filigree and classical micropapillary (cMIP) pattern on FS was investigated. RESULTS: The diagnostic sensitivity of the MIP pattern on FS increased from 43.2% to 65.3% and 56.8% to 81.1% in the study cohort and validation cohort, respectively, and both with good specificity. Filigree not only increased the sensitivity of identifying MIP when there was an absence of cMIP, but also increased the sensitivity when the presence of a minor amount of cMIP. The almost perfect agreement among five pathologists was reached on cMIP and substantial agreement was reached on the filigree in the two cohorts. Moreover, the cMIP and filigree were both correlated with poorer recurrence-free survival (pcMIP = 0.003; pfiligree = 0.032) and overall survival (pcMIP = 0.004; pfiligree = 0.005). CONCLUSIONS: The identification of a filigree may improve the diagnostic sensitivity of the MIP pattern on FS. FS was feasible for the detection of filigree and cMIP patterns in stage T1 lung adenocarcinomas.

Comparison of Bronchial Sleeve Lobectomy With Pulmonary Arterioplasty Versus Pneumonectomy.

BACKGROUND: This study evaluated the efficacy of bronchial sleeve lobectomy with pulmonary arterioplasty compared with pneumonectomy in centrally located non-small cell lung cancer with bronchovascular invasion. METHODS: The cohort consisted of 212 patients receiving pneumonectomy and 156 patients undergoing bronchial sleeve lobectomy with pulmonary arterioplasty. Propensity score matching was used to create a fully balanced cohort, after which, baseline characteristics, perioperative performance, and oncologic results were compared between the 2 groups. RESULTS: A total of 139 pneumonectomy patients were matched with 139 sleeve lobectomy patients. In the matched cohort, bronchial sleeve lobectomy with pulmonary arterioplasty was associated with longer operative time (P < .001), decreased perioperative transfusion rate (P = .002), shorter postoperative hospital stays (P < .001), shorter intensive care unit stays (P = .040), and lower Clavien-Dindo Classification (P = .016). In respect to survival outcomes, a log-rank test revealed no significant difference in overall survival (P = .381) and recurrence-free survival (P = .619) between the 2 surgical procedures. CONCLUSIONS: Bronchial sleeve lobectomy with pulmonary arterioplasty could achieve superior perioperative outcomes and equivalent oncologic efficacy compared with pneumonectomy, indicating that this complex procedure is safe and reliable for centrally located non-small cell lung cancer concurrently involving the pulmonary artery and bronchus.

A novel protein encoded by circASK1 ameliorates gefitinib resistance in lung adenocarcinoma by competitively activating ASK1-dependent apoptosis.

Acquired resistance to growth factor receptor tyrosine kinase inhibitors limits the therapeutic benefits gained by EGFR-mutant lung adenocarcinoma (LUAD) patients treated with gefitinib. Circular RNAs (circRNAs) are novel noncoding RNAs implicated in the regulation of chemoresistance in malignancies. However, whether circRNAs participate in the development of EGFR-TKI resistance in LUAD remains to be clarified. Here, we report that circASK1 (hsa_circ_0007798) is significantly downregulated in gefitinib-resistant cells and enhances the gefitinib sensitivity of LUAD cells. Mechanistically, we identified a novel protein encoded by circASK1, ASK1-272a.a, which is essential for ASK1/JNK/p38 signaling activation and mediates the chemosensitivity-inducing effect of circASK1 in LUAD. Importantly, this novel isoform competes with ASK1 for binding to Akt1, therefore antagonizing Akt1-induced ASK1 phosphorylation and inactivation, leading to the activation of ASK1-induced apoptosis and alleviating gefitinib resistance. Moreover, increased YTHDF2-mediated endoribonucleolytic cleavage of m6A-modified circASK1 accounts for its downregulation in gefitinib-resistant cells. The clinical data and in vivo model further corroborated the suppressive effect of circASK1 and its encoded protein on gefitinib resistance. Our study provides a novel therapeutic target to overcome gefitinib resistance in LUAD patients.

Lobectomy Can Improve the Survival of Patients With Non-small Cell Lung Cancer With Lung Oligometastatic.

Background: This study was to evaluate the value of lobectomy in the prognosis of Non-small cell lung cancer (NSCLC) patients with primary metastasis based on the Surveillance Epidemiology and End Results (SEER) database. Methods: This was a population-based retrospective study and the clinical data were collected from the National Cancer Institute's SEER database between 2010 and 2015. The effects of pulmonary surgery and surgical procedures on lung cancer-specific survival (LCSS) and overall survival (OS) were assessed, and the COX regression models were employed to evaluate the survival of primary surgery in patients with primary metastatic NSCLC (pmNSCLC) and the survival of surgical procedure in pmNSCLC patients. Results: A total of 55,717 patients diagnosed with pmNSCLC between 2010 and 2015 were enrolled, and pulmonary surgery was indicated in 1,575 (2.83%) patients. Surgery was an independent risk factor for LCSS (P < 0.001, HR 0.658, 95%CI: 0.637-0.680) and OS (P < 0.001, HR 0.665, 95%CI: 0.644-0.686) of pmNSCLC patients. The surgery was associated with better OS (P < 0.001, HR 0.678, 95%CI: 0.657-0.699). The site of metastasis was also related to the survival after primary tumor surgery (P = 0.001). As compared to the sublobectomy and pneumonectomy, lobectomy improved the LCSS for NSCLC patients with single-organ metastasis, rather than multiple metastases (P < 0.001). In patients receiving sublobectomy, lobectomy, and pneumonectomy, the median LCSS was 12, 28, and 13 months, respectively, and the 5-year LCSS rate was 14.39, 32.06, and 17.24%, respectively. Conclusion: The effect of locoregional surgery on the survival of pmNSCLC patients with single-organ metastasis has been underestimated, and lobectomy may be a preferred treatment for patients with single-lung metastasis.