Complications In Lung Cancer Patients Research Articles

Effects of thoracoscopic lobectomy on surgical wound infection in patients with lung cancer: A meta‐analysis

AbstractThis meta‐analysis systematically evaluates the impact of thoracoscopic lobectomy on wound infection and complications in lung cancer patients. An extensive computerized search was conducted using PubMed, Embase, Google Scholar, Cochrane Library, China National Knowledge Infrastructure and Wanfang databases for studies comparing thoracoscopic lobectomy with open thoracotomy in the treatment of lung cancer, covering the period up to September 2023. Two researchers independently screened the literature, extracted data and assessed the quality according to predefined inclusion and exclusion criteria. Data analysis was performed using Stata 17.0 software. Ultimately, 21 studies involving 2118 lung cancer surgery patients were included. The analysis revealed that thoracoscopic lobectomy significantly reduced the incidence of wound infections (odds ratio [OR] = 0.22, 95% confidence interval [CI]: 0.13–0.37, p < 0.001) and complications (OR = 0.27, 95% CI: 0.21–0.36, p < 0.001) in lung cancer surgery patients, and also significantly shortened hospital stays (standardized mean difference = −2.07, 95% CI: −2.39 to −1.76, p < 0.001). This study indicates that compared with conventional open thoracotomy, thoracoscopic lobectomy in the treatment of lung cancer reduces the incidence of wound infections and complications and shortens hospital stays, demonstrating significant therapeutic efficacy and warranting broader clinical application.

Lung Cancer Related Thrombosis (LCART): Focus on Immune Checkpoint Blockade.

Cancer-associated thrombosis (CAT) is a common complication in lung cancer patients. Lung cancer confers an increased risk of thrombosis compared to other solid malignancies across all stages of the disease. Newer treatment agents, including checkpoint immunotherapy and targeted agents, may further increase the risk of CAT. Different risk-assessment models, such as the Khorana Risk Score, and newer approaches that incorporate genetic risk factors have been used in lung cancer patients to evaluate the risk of thrombosis. The management of CAT is based on the results of large prospective trials, which show similar benefits to low-molecular-weight heparins (LMWHs) and direct oral anticoagulants (DOACs) in ambulatory patients. The anticoagulation agent and duration of therapy should be personalized according to lung cancer stage and histology, the presence of driver mutations and use of antineoplastic therapy, including recent curative lung surgery, chemotherapy or immunotherapy. Treatment options should be evaluated in the context of the COVID-19 pandemic, which has been shown to impact the thrombotic risk in cancer patients. This review focuses on the epidemiology, pathophysiology, risk factors, novel predictive scores and management of CAT in patients with active lung cancer, with a focus on immune checkpoint inhibitors.

Effect of segmental versus lobectomy in minimally invasive surgery on postoperative wound complications in lung cancer patients: A meta-analysis.

It is still a matter of debate whether the surgical segmentectomy and lobectomy of lung cancer are comparable in the incidence of perioperative wound complications. An extensive review of the literature through August 2023 was carried out with a critical review of four databases. Following the acceptance and elimination criteria set out in the trial, as well as a qualitative assessment of the literature, this resulted in a review of related research that compared the results of both lobectomy and partial resection in the management of lung cancer. The analysis of the data was performed with the RevMan 5.3 software, and the 95% confidence interval [CI] and odds ratio [OR] were performed with either stationary or random-effect models. It is concluded that the operation time of lobectomy is shorter than that of sectioning in the treatment of segmentectomy (mean difference [MD], -38.62; 95% CI, -41.96, -35.28; p < 0.0001). But the rate of postoperative wound infection (OR, 0.62; 95% CI, 0.18, 2.15; p = 0.45) and intraoperative blood loss (MD, 17.54; 95% CI, -4.19, 39.26; p = 0.11) were not significantly different for them. Thus, for those who have received a pulmonary carcinoma operation, different operative methods might not have an impact on the incidence of postoperative wound infections. The operative procedure appears to have a major impact on the length of the operation in patients.

Potential of bacteriophage therapy in managing Staphylococcus aureus infections during chemotherapy for lung cancer patients

Respiratory Staphylococcus aureus infection represents a common complication in lung cancer patients, which is characterized with progressively and recurrently intratumor invasion. Although bacteriophages are widely reported as an effective bioweapon for managing bacterial infections, its applicability in handling infectious complications during cancer chemotherapy remains unknown. In this work, we hypothesized cancer chemotherapeutics would influence the efficacy of bacteriophages. To verify this end, interactions between four anticancer drugs (Gemcitabine, Doxorubicin, Cisplatin, and Irinotecan) with phage K were investigated, where Cisplatin directly reduced phage titers while Gemcitabine and Doxorubicin partially inhibited its propagation. The antibacterial efficacy of drug-phage K combinations was tested in a S. aureus infected cancer cell model. Doxorubicin enhanced the antibacterial capacity of phage K, destroying 22-folds of cell-associated bacteria than that of phage K alone use. Also, S. aureus migration was remarkably reduced by Doxorubicin. Overall, our data suggested that Doxorubicin had synergistic effects with phage K in combating S. aureus intracellular infection and migration. This work may broaden the options of indication for phage clinical transformation and also provide reference for the adjunctive application of chemo drugs in intracellular infection management.

Analysis of the Incidence of Lower Limb Deep Venous Thrombosis and Its Related Risk Factors in the Postoperative Patients with Lung Cancer

Lung cancer is the first leading cause of morbidity and mortality among the malignant tumors, which has become a hot issue in current research. Clinically, lung cancer is divided into small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC) according to the pathological types. NSCLC includes adenocarcinoma, squamous cell carcinoma and other types of lung cancer, accounting for about 80% of all lung cancer. Venous thromboembolism (VTE) includes deep venous thrombosis (DVT) and pulmonary embolism (PE), which is a recognized complication in lung cancer patients with higher morbidity and mortality. The aim of this study is to determine the incidence of DVT and reveal the risk factors for DVT in the postoperative patients with lung cancer. We collected 83 postoperative patients with lung cancer admitted to the Department of Lung Cancer Surgery, Tianjin Medical University General Hospital from December 2021 to December 2022. All these patients were examined by color Doppler ultrasound of lower extremity vein upon admission and after operation to analyze the incidence of DVT. In order to explore the possible risk factors for DVT in these patients, we further analyzed the correlations between DVT and their clinical features. At the same time, the changes of coagulation function and platelet were monitored to investigate the value of blood coagulation in the patients with DVT. DVT occurred in 25 patients after lung cancer operation, and the incidence rate of DVT was 30.1%. Further analysis found that the incidences of postoperative lower limb DVT were higher in lung cancer patients of stage III+IV or over 60 years of age (P=0.031, P=0.028). D-Dimer level in patients with thrombosis was significantly higher than that in non-thrombus patients on the 1st, the 3rd, and the 5th day after operation (P<0.05), and there was no significant difference in platelets and fibrinogen (FIB) (P>0.05). The overall incidence of DVT in our center after lung cancer patients operation was 30.1%. Late-stage and older postpatients were more likely to develop DVT, and these patients with higher D-Dimer values should be considered the possibility of VTE events.

Reducing Post-Operative Alveolo-Pleural Fistula by Applying PGA-Sheets (Neoveil) after Major Lung Resection: A Historical Case-Control Study.

Alveolo-pleural fistula remains a serious post-operative complication in lung cancer patients after surgery, which is associated with prolonged hospital stay and higher healthcare costs. The aim of this study is to evaluate the efficacy of a polyglycol acid (PGA)-sheet known as Neoveil in preventing post-operative air-leak in cases of detected intra-operative air-leak after lung resection. Between 11/2021 and 7/2022, a total of 329 non-small cell lung cancer (NSCLC) patients were surgically treated in two institutions. Major lung resections were performed in 251 cases. Among them, 44 patients with significant intra-operative air-leak at surgery were treated by reinforcing staple lines with Neoveil (study group). On the other hand, a historical group (selected by propensity score matched analysis) consisting of 44 lung cancer patients with significant intra-operative air leak treated by methods other than the application of sealant patches were considered as the control group. The presence of prolonged air-leak (primary endpoint), pleural drainage duration, hospital stay, and post-operative complication rates were evaluated. The results showed that prolonged air-leak (>5 days after surgery) was not observed in study group, while this event occurred in four patients (9.1%) in the control group. Additionally, a substantial reduction (despite not statistically significant) in the chest tube removal was noted in the study group with respect to the control group (3.5 vs. 4.5, p = 0.189). In addition, a significant decrease in hospital stay (4 vs. 6 days, p = 0.045) and a reduction in post-operative complications (2 vs. 10, p = 0.015) were observed in the study group when compared with the control group. Therefore, in cases associated with intra-operative air-leak after major lung resection, Neoveil was considered a safer and more effective aerostatic tool and represents a viable option during surgical procedures.

Treatment of brain metastases in lung cancer

Lung cancer is the most frequent oncological disorder and has been the main topic in most oncological congresses. There have been countless changes in diagnosis and treatment, improvements in the diagnostic methods, more effective and less invasive curative care and improvements in systemic treatments (new drugs and molecular targets). In the whole therapeutic spectrum, radiotherapy plays a significant role and at the brain metastasis level the changes are very relevant. Brain metastases are the most frequent neuro-oncologic complication in lung cancer patients. Managing this situation has become increasingly complex in recent years. The results have been improving, not only in terms of responses to treatment but also in terms of an increasing reduction in side effects. This paper reviews the latest advances and current management of patients with brain metastases from lung cancer.

Automated 3D segmentation of the aorta and pulmonary artery for predicting outcomes after thoracoscopic lobectomy in lung cancer patients.

Preoperative two-dimensional manual measurement of pulmonary artery diameter in a single-cut axial view computed tomography (CT) image is a commonly used non-invasive prediction method for pulmonary hypertension. However, the accuracy may be unreliable. Thus, this study aimed to evaluate the correlation of short-term surgical outcomes and pulmonary artery/aorta (PA/Ao) diameter ratio measured by automated three-dimensional (3D) segmentation in lung cancer patients who underwent thoracoscopic lobectomy. We included 383 consecutive lung cancer patients with thin-slice CT images who underwent lobectomy at a single institute between January 1, 2011 and December 31, 2019. Automated 3D segmentation models were used for 3D vascular reconstruction and measurement of the average diameters of Ao and PA. Propensity-score matching incorporating age, Charlson comorbidity index, and lobectomy performed by uniportal VATS was used to compare clinical outcomes in patients with PA/Ao ratio ≥1 and those <1. Our segmentation method measured 29 (7.57%) patients with a PA/Ao ratio ≥1. After propensity-score matching, a higher overall postoperative complication classified by the Clavien-Dindo classification (p = 0.016) were noted in patients with 3D PA/Ao diameter ratio ≥1 than those of <1. By multivariate logistic regression, patients with a 3D PA/Ao ratio ≥ 1 (p = 0.013) and tumor diameter > 3cm (p = 0.002) both significantly predict the incidence of postoperative complications. Pulmonary artery/aorta diameter ratio ≥ 1 measured by automated 3D segmentation may predict postoperative complications in lung cancer patients who underwent lobectomy.

Clinical outcome and risk factors for subcutaneous emphysema in patients with lung cancer after video-assisted thorascopic surgery.

Background and purposeWith the clinical application of minimally invasive surgery and concept of enhanced recovery after surgery, the incidence of postoperative complications in lung cancer patients has been significantly reduced. However, postoperative subcutaneous emphysema (SE) becomes the main factor affecting the early discharge of patients. The aim of this study was to analyze the clinical outcome and risk factors for postoperative SE in lung cancer patients.MethodsThe clinical data of 414 lung cancer patients who were admitted to the Department of Thoracic Surgery, West China Hospital, Sichuan University from September 2021 to December 2021 were prospectively collected. The incidence, severity and treatment of patients who had SE, surgery approach, application of drainage tube and clinical information were analyzed.ResultsThe incidence rate of postoperative SE in patients with lung cancer was 33.09% (137/414) and mild cases accounted for the vast majority (30.19%, 125/414). Multivariate analysis indicated that male [odds ratio (OR) = 2.247, P = .014] and advanced age (OR = 1.021, P = .043) were main risk factors for postoperative SE in patients with lung cancer. Conservative treatment was the main treatment option for SE (98.5%, 135/137). The average hospital stay in the subcutaneous emphysema group (5.49 ± 4.41 days) was significantly longer than that in the non-subcutaneous emphysema group (4.44 ± 3.32 days) (P = .014) and no significant statistical difference in the average total hospital cost between the two groups (7,798.31 ± 1,414.85$ vs. 7,501.14 ± 1,605.18$, P = .072).ConclusionPostoperative SE in patients with minimally invasive lung cancer is mainly mild, and conservative treatment is appropriate for most cases.

The Diagnostic Value of the Systemic Immune-Inflammation Index for Venous Thromboembolism in Lung Cancer Patients: A Retrospective Study

Background Venous thromboembolism (VTE) is considered a common complication in lung cancer patients. Despite its widespread use, the Khorana score performed moderately in predicting VTE risk. This study aimed to determine the diagnostic utility of the Systemic Immunoinflammatory Index (SII) and to create a novel nomogram for predicting VTE in patients with pulmonary carcinoma. Materials and Methods The data, like clinical features and laboratory indicators, of inpatients diagnosed with lung cancer from March 2019 to March 2020 were collected and analyzed. Univariate and multivariate logistic analyses were performed to confirm the risk factors and then construct a nomogram model. The calibration curve and clinical decision curve analysis (DCA) were used to assess the model's fitting performance. The receiver-operating characteristic (ROC) curve and the area under the ROC curve (AUC) were used to evaluate the diagnostic value of SII and the nomogram. Results This study enrolled 369 lung patients with a VTE morbidity rate of 23.33%. The patients with VTE had higher SII levels than the non-VTE group (1441.47 ± 146.28 vs. 626.76 ± 26.04, P < 0.001). SII is the stronger correlator for VTE among inflammatory markers, of which the optimal cut-off value was 851.51. Univariate and multivariate analysis revealed that the age, metastasis, antitumor treatment, hemoglobin<100 g/L, SII>851.51 × 109/L, and D-dimer>2 folds were independent risk factors for lung cancer-related VTE, and a new prediction nomogram model was constructed based on them. ROC curve analysis showed the AUC of the new model and Khorana score were 0.708 (0.643-0.772) and 0.600 (0.531-0.699). Conclusion The SII was a simple and valuable biomarker for VTE, and the new nomogram model based on it can accurately forecast the occurrence of VTE. They can be utilized in clinical practice to identify those at high risk of VTE in lung cancer patients.

The efficacy of pulmonary rehabilitation exercise training on complications and mortality after lung cancer resection: a systematic review and meta-analysis.

BackgroundThe efficacy of pulmonary rehabilitation exercise training for patients after lung cancer resection has been controversial. We sought to evaluate the efficacy of pulmonary rehabilitation on the incidence of complications and mortality in patients after lung cancer resection.MethodsSearch English databases PubMed, EMBASE, Medline to obtain literature. The literature compared the effect of pulmonary rehabilitation exercise training intervention or not on the efficacy of patients after lung cancer resection, and the outcomes included postoperative complications and mortality. The quality of the included literature was assessed according to the Cochrane risk of bias assessment work. The chi-square test was used to test for heterogeneity. When there is heterogeneity, a random effect model is used; when there is no heterogeneity, a fixed effect model is used.ResultsA total of 9 prospective clinical studies (comprising 1,338 patients) were included in this meta-analysis. Among the patients, there were 571 cases in the rehabilitation group and 767 cases in the control group. The incidence of postoperative complications in the rehabilitation group was lower than that in the control group. The odds ratio (OR) value was 0.66 and 95% confidence interval (CI) was 0.47–0.94 (P=0.02). There was no heterogeneity among studies and no publication bias. The incidence of postoperative pulmonary complications in the rehabilitation group was lower than that in the control group, OR =0.33 (95% CI: 0.22–0.50) (P<0.00001). There was no heterogeneity among studies and no publication bias. There was no significant difference in postoperative mortality between the 2 groups (OR =0.77; 95% CI: 0.26–2.30; P=0.65). There was no heterogeneity among studies and no publication bias.DiscussionImplementing pulmonary rehabilitation significantly reduced postoperative complications and the risk of pulmonary complications in lung cancer patients, but had no significant effect on mortality. Pulmonary rehabilitation exercise training is recommended for patients undergoing lung cancer resection.

The Predictive Value of Stair Climbing Test on Postoperative Complications in Lung Cancer Patients with Limited Pulmonary Function.

To evaluate the predictive value of stair climbing test (SCT) on postoperative complications in lung cancer patients with limited pulmonary function. A total of 727 hospitalized lung cancer patients with limited pulmonary function were retrospectively reviewed. Included in the cohort were 424 patients who underwent SCT preoperatively. Patients were grouped according to general condition, past medical history, surgical approach, pulmonary function test, and SCT results. Comparison of the postoperative cardiopulmonary complication rates was made and independent risk factors were identified. A total of 89 cardiopulmonary-related complications occurred in 69 cases, accounting for 16.3% of the entire cohort. The postoperative cardiopulmonary complication rates were significantly different between groups stratified by smoking index, percentage of forced expiratory volume in one second, percentage of diffusion capacity for carbon monoxide, SCT results, excision extension, and anesthetic duration (p <0.05). Multivariate analysis showed that only height achieved (p <0.001), changes in heart rate (∆HR; p <0.001), and excision extension (p = 0.006) were independent risk factors for postoperative cardiopulmonary complications. The SCT could be used as a preoperative screening method for lung cancer patients with limited pulmonary function. For those patients who could only climb less than 6 floors or had ∆HR >30 bpm in the test, sublobar resection should be selected to reduce the postoperative cardiopulmonary complication rate.

Profile of metastatic lung cancer patients susceptible to development of thromboembolism during immunotherapy

BackgroundThromboembolism (TE) is a serious complication in lung cancer patients; however, risk factors for developing TE during treatment with immuno-oncology (IO) drugs are unclear. Materials and methodsA retrospective study of lung cancer patients hospitalized in Tokyo Medical and Dental University was performed to clarify the association between TE and systemic therapy, especially IOs. Patients were divided into an IO cohort, a chemotherapy cohort (CT cohort), and a control cohort (patients without recurrence after surgery). Association studies of variables relevant to TE were performed. ResultsA total of 592 patients were enrolled (IO cohort, 120; CT cohort, 294; control cohort, 178). Eight patients (6.7%) in the IO cohort, seven (2.4%) in the CT cohort, and three (1.7%) in the control cohort developed TE. Least Absolute Shrinkage and Selection Operator (LASSO) regression analysis identified IO, a history of TE, poor performance status (PS), and prior anticoagulation therapy as being associated with TE. Subsequent multivariate logistic regression analysis identified a history of TE (odds ratio (OR), 6.03; 95% confidence interval (CI), 2.09–17.40; P = 0.01) and poor PS (OR, 3.84; 95% CI, 1.34–11.00; P < 0.001) as potential risk factors for developing TE. The incidence of TE in the IO cohort patients with both of these characteristics was significantly higher (OR, 52.82; 95% CI, 6.72–506.37; P < 0.001) than that in the control cohort. ConclusionLung cancer patients with a history of TE and poor PS are at increased risk of TE during treatment with IOs. Micro abstractThe profiles of lung cancer patients susceptible to development of thromboembolism (TE) during immunotherapy are unclear, even though TE is associated with a worse prognosis. Here, association studies of variables relevant to TE revealed that patients with a history of TE and poor performance status are at higher risk of developing TE during immunotherapy.

MicroRNA-106a regulates autophagy-related cell death and EMT by targeting TP53INP1 in lung cancer with bone metastasis

Bone metastasis is one of the most serious complications in lung cancer patients. MicroRNAs (miRNAs) play important roles in tumour development, progression and metastasis. A previous study showed that miR-106a is highly expressed in the tissues of lung adenocarcinoma with bone metastasis, but its mechanism remains unclear. In this study, we showed that miR-106a expression is dramatically increased in lung cancer patients with bone metastasis (BM) by immunohistochemical analysis. MiR-106a promoted A549 and SPC-A1 cell proliferation, migration and invasion in vitro. The results of bioluminescence imaging (BLI), micro-CT and X-ray demonstrated that miR-106a promoted bone metastasis of lung adenocarcinoma in vivo. Mechanistic investigations revealed that miR-106a upregulation promoted metastasis by targeting tumour protein 53-induced nuclear protein 1 (TP53INP1)-mediated metastatic progression, including cell migration, autophagy-dependent death and epithelial–mesenchymal transition (EMT). Notably, autophagy partially attenuated the effects of miR-106a on promoting bone metastasis in lung adenocarcinoma. These findings demonstrated that restoring the expression of TP53INP1 by silencing miR-106a may be a novel therapeutic strategy for bone metastatic in lung adenocarcinoma.

Continuous Serratus Anterior Plane Block Improved Early Pulmonary Function After Lung Cancer Surgical Procedure

BackgroundSerratus anterior plane block (SAPB) has been proven to be an efficient way to control postoperative pain. This study explored whether the use of continuous SAPB in combination with flurbiprofen could improve early pulmonary function in lung cancer patients undergoing video-assisted thoracoscopic surgery (VATS). MethodsFrom July 2019 to April 2020, patients who scheduled for elective lung resection undergoing VATS were randomly allocated to receive patient-controlled SAPB in combination with intravenous flurbiprofen or patient-controlled intravenous analgesia. Postoperative pulmonary function variables, including forced expiratory volume in 1 second, and forced vital capacity were collected before and 24, 48, and 72 hours after Surgical Procedure. Pain intensity was measured at rest and on coughing. Comfort scores during breathing exercises, postoperative pulmonary complications, and adverse events were recorded. ResultsA substantial reduction in lung function was exhibited in both groups after Surgical Procedure (P < .001), but lung function variables in the continuous SAPB group were significantly higher (P < .001) throughout the postoperative period up to 72 hours, regardless of the surgical procedure type. Meanwhile, there were significant differences of pain intensity at rest and on coughing between the groups (P < .001). The incidence of pneumonia, pulmonary atelectasis, hypoxemia, vomiting, and the comfort score in the continuous SAPB group was significantly lower (P < .05). ConclusionsPostoperative acute pain treatment with continuous SAPB in combination with flurbiprofen enhanced pulmonary function and reduced postoperative pulmonary complications in lung cancer patients undergoing VATS.

Analysis of Risk Factors Related to Complications of Puncture Biopsy in Lung Cancer Patients Under Image Guidance

To investigate the risk factors of complications in lung cancer patients after CT image-guided percutaneous lung biopsy (PTNB), in this study, 110 patients admitted to Xixi Hospital from January 30, 2017 to June 30, 2019 were selected for PTNB, and the basic characteristic information, lesion diameter, number of needle penetration, depth of needle penetration, physiological results of biopsy, postoperative concurrent symptoms, and success rate of biopsy were recorded. In addition, multivariate Logistic regression model (MLRM) was adopted to explore the correlation between various correlated characters and concurrent symptoms. The results showed that the biopsy pathological results were 53 cases of adenocarcinoma, 31 patients with squamous cell carcinoma, 8 patients with thymic carcinoma, 7 patients with small cell carcinoma and 11 patients with lymph carcinoma, and the success rate of needle biopsy was 100% by comparison with the final diagnosis. Among them, 35 patients developed pneumothorax symptoms postoperatively with a complication rate of 31.82%, 22 patients developed hemoptysis postoperatively with a complication rate of 20%, and 6 patients developed infection with a complication rate of 5.45%. The results of regression analysis showed that pneumothorax and hemoptysis were positively correlated with the number of de needles (P &lt; 0.05), and negatively correlated with lesion diameter (P &lt; 0.05). In addition, pneumothorax was also significantly positively correlated with age (P &lt; 0.05), and infection was significantly positively correlated with the number of puncture needles (P &lt; 0.05). Therefore, the main complications after PTNB are pneumothorax and hemoptysis, the high risk factors associated with pneumothorax include lesion diameter, number of puncture needles and age, the high risk factors associated with hemoptysis include lesion diameter and number of puncture needles, and the risk factors associated with infection are number of puncture needles.

Lung Cancer Cell-Derived Secretome Mediates Paraneoplastic Inflammation and Fibrosis in Kidney in Mice.

Simple SummaryParaneoplastic nephrotic syndrome is a complication arising in lung cancer patients. In the present study, we established an LLC1 cell orthotopic xenograft C57BL/6 mice model to translation paraneoplastic nephrotic syndrome (PNS). The pathological aspects of PNS were characterized in TGF-β signaling-engaged renal fibrosis, and renal inflammation with IL-6 expression in kidney. To reveal how the lung cancer cells remotely drive pathogenic progression, secretome derived from LLC1 cells and A549 cells were proteomically profiled. Additionally, the secretome profiling was subjected to diseases and biofunctions assessment by Ingenuity Pathway analysis (IPA). As matter of secretome profiling and IPA prediction, the Fibronectin, C1r, and C1s are potential of nephrotoxicity linked to paraneoplastic effects on glomerular pathogenesis in these lung cancer mice.Kidney failure is a possible but rare complication in lung cancer patients that may be caused by massive tumor lysis or a paraneoplastic effect. Clinical case reports have documented pathological characteristics of paraneoplastic syndrome in glomeruli, but are short of molecular details. When Lewis lung carcinoma 1 (LLC1) cells were implanted in mice lungs to establish lung cancer, renal failure was frequently observed two weeks post orthotopic xenograft. The high urinary albumin-to-creatinine ratio (ACR) was diagnosed as paraneoplastic nephrotic syndrome in those lung cancer mice. Profiling the secretome of the lung cancer cells revealed that the secretory proteins were potentially nephrotoxic. The nephrotoxicity of lung cancer-derived secretory proteins was tested by examining the pathogenic effects of 1 × 106, 2 × 106, and 5 × 106 LLC1 cell xenografts on the pathogenic progression in kidneys. Severe albuminuria was present in the mice that received 5 × 106 LLC1 cells implantation, whereas 106 cell and 2 × 106 cell-implanted mice have slightly increased albuminuria. Pathological examinations revealed that the glomeruli had capillary loop collapse, tumor antigen deposition in glomeruli, and renal intratubular casts. Since IL-6 and MCP-1 are pathologic markers of glomerulopathy, their distributions were examined in the kidneys of the lung cancer mice. Moderate to severe inflammation in the kidneys was correlated with increases in the number of cells implanted in the mice, which was reflected by renal IL-6 and MCP-1 levels, and urine ACR. TGF-β signaling-engaged renal fibrosis was validated in the lung cancer mice. These results indicated that lung cancer cells could provoke inflammation and activate renal fibrosis.

Clinicopathological features, risk and survival in lung cancer survivors with therapy-related acute myeloid leukaemia

BackgroundA secondary malignancy is the most serious complication in lung cancer (LC) survivors. This study aimed to evaluate the clinicopathological features, predictable risk factors and survival of patients with LC who developed therapy-related acute myeloid leukaemia (t-AML).MethodsPatients from the Surveillance, Epidemiology, and End Results (SEER) database diagnosed with t-AML after LC between 1975 and 2015 were included. Standardized incidence ratios (SIRs) were used to perform multiple primary analyses. The risk of t-AML development among LC patients was assessed using a logistic regression model. Kaplan–Meier analysis was used to construct overall survival (OS) curves. Cox regression was used to assess the influence of various prognostic factors.ResultsA total of 104 patients with t-AML after LC-targeting chemotherapy were included. The median latency period to the development of t-AML was 35.5 months. The calculated SIR of t-AML was 4.00. Chemoradiotherapy, small cell lung cancer (SCLC), or localized/regional-stage LC was a risk factor for the development of t-AML. The median OS was only 1 month, and those younger than 65 years were predicted to have a better OS time.Conclusionst-AML is a rare but serious late complication in LC patients and is associated with a poor prognosis. It is necessary to carry out long-term follow-up and screen for t-AML in LC patients, especially among those undergoing both radiotherapy and chemotherapy, with SCLC or with localized/regional-stage LC.

79 PREOPERATIVE TOBACCO CESSATION AND MAJOR POSTOPERATIVE MORBIDITY IN PATIENTS UNDERGOING ESOPHAGECTOMY

Abstract While preoperative tobacco cessation has been associated with decreased pulmonary complications in lung cancer patients in the postoperative period, this relationship has not been explored among patients undergoing esophagectomy in this era of increasingly prevalent tobacco cessation campaigns and enhanced recovery after surgery. Methods We reviewed ever-smokers who underwent esophagectomy at a single institution from January 2004 through June 2019 for esophageal cancer. Occurrence of Clavien-Dindo classification ≥3 major postoperative morbidity (MPM), including anastomotic leak, chylothorax, reoperation, organ dysfunction, respiratory failure, and ICU readmission was calculated. In an effort to evaluate an effect of smoking cessation on outcome, never-smokers were excluded from analyses. Multivariable logistic regression with backwards stepwise elimination was completed to determine the optimal cessation interval associated with reduction in MPM. Robust standard errors were used to account for clustering among surgeons. Results 725 patients met inclusion criteria, including 666 (92%) with adenocarcinoma and a smaller proportion with squamous cell carcinoma. Most patients were male (650, 90%), and the median age was 63 years (IQR 57–69). Records showed that 505 patients (60%) had quit &amp;gt;5 years prior to esophagectomy, and 82 (11%) were current smokers or had quit within the month preceding esophagectomy. MPM occurred in 213 (29%). After univariate regression, age, gender, pack-year history, operative duration, and FEV1 were included in a multivariable model. While age remained associated wtih MPM, preoperative tobacco cessation of any interval was not associated with outcomes. Conclusion Our previous publication showed increased complication risk for smokers undergoing esophagectomy compared to non-smokers. However, among ever-smokers, no specific interval of preoperative cessation demonstrated decreased MPM. In a setting of active tobacco cessation programs, patients who have not completely achieved abstinence may still be offered surgery with equivalent perioperative outcomes.

Effect of malignant-associated pleural effusion on endothelial viability, motility and angiogenesis in lung cancer.

Malignant pleural effusion (MPE) and paramalignant pleural effusion (PPE) remain debilitating complications in lung cancer patients with poor prognosis and limited treatment options. The role of vascular endothelial cells has not been explored in the pleural environment of lung cancer. By integrating MPE and PPE as malignant‐associated pleural fluid (MAPF), the current study aimed to evaluate the effect of MAPF on cell proliferation, migration and angiogenesis of HUVEC. First, increased capillaries were identified in the subpleural layer of lung adenocarcinoma. Compatible with pathological observations, the ubiquitous elevation of HUVEC survival was identified in MAPF culture regardless of the underlying cancer type, the driver gene mutation, prior treatments and evidence of malignant cells in pleural fluid. Moreover, MAPF enhanced HUVEC motility with the formation of lamellipodia and filopodia and focal adhesion complex. Tube formation assay revealed angiogenic behavior with the observation of sheet‐like structures. HUVEC cultured with MAPF resulted in a significant increase in MAPK phosphorylation. Accompanied with VEGFR2 upregulation in MAPF culture, there was increased expressions of p‐STAT3, HIF‐1α and Nf‐kB. VEGF/VEGFR2 blockade regressed endothelial migration and angiogenesis but not cell proliferation. Our data indicate the angiogenic activities of MAPF on vascular endothelial cells that revealed increased pleural capillaries in lung cancer. Targeting the VEGF/VEGFR2 pathway might modulate the angiogenic propensity of MAPF in future clinical investigations.