Acute cardiac tamponade after Endostar treatment of non-small cell lung cancer: A case report.

RATIONALE: Recombinant human endostatin (Endostar) is extensively utilized in China for the clinical management of patients with driver gene-negative non-small cell lung cancer (NSCLC) at stage TNM IV. This report describes the case of a lung cancer patient treated exclusively with Endostar maintenance therapy, who experienced a rapid deterioration in respiratory function. PATIENT CONCERNS: The case involved a patient with a pathologically confirmed squamous cell carcinoma of the left lung, treated in our department. Following 1 month of albumin-bound paclitaxel chemotherapy and localized radiotherapy for the left lung lesion, the patient initiated treatment with a single agent, Endostar 30mg, on October 19, 2021. The medication was administered via intravenous infusion over a 7 days. DIAGNOSIS: On October 23, 2021, the patient exhibited symptoms of chest constriction, discomfort, coughing, and sputum production. By October 28, the patient presented with pronounced dyspnea and respiratory distress. An emergency CT scan detected pericardial tamponade and significant deviations in several blood parameters from pretreatment values. INTERVENTIONS: Percardial puncture and catheter drainage were recommended as therapeutic intervention. OUTCOMES: Considering the patient advanced age, the patient and their family opted to refuse this medical procedure, leading to the patient unfortunate demise on November 2, 2021. LESSONS: Medical professionals should remain vigilant for the potential, albeit rare, risk of Endostar inducing acute pericardial tamponade, a severe and potentially fatal complication.

Interstitial Lung Abnormalities.

Interstitial lung abnormalities (ILA) is a radiographic term, which has recently undergone clarification of definition with creation of 3 subtypes. ILA is defined as incidental identification of computed tomography abnormalities in a patient who is not suspected of having an interstitial lung disease (ILD). A subset of ILA may progress to clinically significant ILD and is associated with morbidities not related to progression such as an increased incidence of sepsis-related acute respiratory distress syndrome (ARDS). ILA has been associated with an increased incidence of treatment-related complications in patients with lung cancer. Information on corresponding histology is limited; knowledge gaps exist concerning optimal patient management.

Current pharmacotherapies for advanced lung cancer with pre-existing interstitial lung disease : A literature review and future perspectives.

Patients with interstitial lung disease (ILD), especially those with idiopathic pulmonary fibrosis, are at increased risk of developing lung cancer (LC). Pharmacotherapy for advanced LC has dramatically progressed in recent years;however, management of LC with pre-existing ILD (LC-ILD) is challenging due to serious concerns about the risk of acute exacerbation of ILD (AE-ILD). As patients with LC-ILD have been excluded from most prospective clinical trials of advanced LC, optimal pharmacotherapy remains to be elucidated. Although the antitumor activity of first-line platinum-based cytotoxic chemotherapy appears to be similar in advanced LC patients with or without ILD, its impact on the survival of patients with LC-ILD is limited. Immune checkpoint inhibitors may hold promise for long-term survival, but many challenges remain, including safety and appropriate patient selection. Further understanding the predictive factors for AE-ILD after receiving pharmacotherapy in LC-ILD may lead to appropriate patient selection and lower treatment risk. The aim of this review was to summarize the current evidence related to pharmacotherapy for advanced LC-ILD and discuss emerging areas of research. J. Med. Invest. 71 : 9-22, February, 2024.

Association between advanced lung cancer inflammation index and all-cause and cardiovascular mortality among stroke patients: NHANES, 1999-2018.

Background: Stroke was a major global public health challenge, and its prognosis was remarkably associated with inflammation levels and nutritional status. The advanced lung cancer inflammation index (ALI) was a comprehensive indicator that combined inflammation and nutritional status. Currently, the relationship between ALI and the prognosis of stroke patients was not yet known. The purpose of the current study was to estimate their relationship. Methods: Cohort data from the National Health and Nutrition Examination Survey (NHANES) 1999-2018 were collected. The association between ALI and all-cause and cardiovascular disease (CVD) mortality in stroke patients was estimated using a multivariable adjusted Cox model. Their non-linear relationship was analyzed by restricted cubic spline analysis. Sensitivity analysis was constructed through stratified analysis and interaction analysis. Results: 1,440 stroke patients were included in this study. An elevated ALI was significantly related to a reduced risk of all-cause mortality in stroke patients but not related to CVD mortality. A reverse J-shaped non-linear association between ALI and all-cause mortality in stroke patients, with an inflection point at 83.76 (the lowest of the mortality risk). On the left side of the inflection point, for each 10 U increase in ALI, there was a 16% reduction in the risk of all-cause mortality. However, on the right side, the risk increased by 6%. There was no remarkable interaction between stratified variables and ALI. Conclusion: This was the first study on the relationship between ALI and all-cause and CVD mortality in stroke patients. Elevated ALI was closely associated with a reduced risk of all-cause mortality. A reverse J-shaped non-linear relationship existed between the two, with an inflection point at 83.76. These findings implied that controlling the ALI of stroke patients within an appropriate range was crucial for their prognosis (such as weight management, albumin supplementation, anti-inflammatory treatment). The dynamic variation in ALI was also advantageous for clinicians in establishing personalized ALI criteria to maximize the long-term survival of stroke patients.

Single-cell transcriptomics reveal metastatic CLDN4+ cancer cells underlying the recurrence of malignant pleural effusion in patients with advanced non-small-cell lung cancer.

BACKGROUND: Recurrent malignant pleural effusion (MPE) resulting from non-small-cell lung cancer (NSCLC) is easily refractory to conventional therapeutics and lacks predictive markers. The cellular or genetic signatures of recurrent MPE still remain largely uncertain. METHODS: 16 NSCLC patients with pleural effusions were recruited, followed by corresponding treatments based on primary tumours. Non-recurrent or recurrent MPE was determined after 3-6 weeks of treatments. The status of MPE was verified by computer tomography (CT) and cytopathology, and the baseline pleural fluids were collected for single-cell RNA sequencing (scRNA-seq). Samples were then integrated and profiled. Cellular communications and trajectories were inferred by bioinformatic algorithms. Comparative analysis was conducted and the results were further validated by quantitative polymerase chain reaction (qPCR) in a larger MPE cohort from the authors' centre (n = 64). RESULTS: The scRNA-seq revealed that 33 590 cells were annotated as 7 major cell types and further characterized into 14 cell clusters precisely. The cell cluster C1, classified as Epithelial Cell Adhesion Molecule (EpCAM)+ metastatic cancer cell and correlated with activation of tight junction and adherence junction, was significantly enriched in the recurrent MPE group, in which Claudin-4 (CLDN4) was identified. The subset cell cluster C3 of C1, which was enriched in recurrent MPE and demonstrated a phenotype of ameboidal-type cell migration, also showed a markedly higher expression of CLDN4. Meanwhile, the expression of CLDN4 was positively correlated with E74 Like ETS Transcription Factor 3 (ELF3), EpCAM and Tumour Associated Calcium Signal Transducer 2 (TACSTD2), independent of driver-gene status. CLDN4 was also found to be associated with the expression of Hypoxia Inducible Factor 1 Subunit Alpha (HIF1A) and Vascular Endothelial Growth Factor A (VEGFA), and the cell cluster C1 was the major mediator in cellular communication of VEGFA signalling. In the extensive MPE cohort, a notably increased expression of CLDN4 in cells from pleural effusion among patients diagnosed with recurrent MPE was observed, compared with the non-recurrent group, which was also associated with a trend towards worse overall survival (OS). CONCLUSIONS: CLDN4 could be considered as a predictive marker of recurrent MPE among patients with advanced NSCLC. Further validation for its clinical value in cohorts with larger sample size and in-depth mechanism studies on its biological function are warranted. TRIAL REGISTRATION: Not applicable.

Lung cancer in older patients with granulomatosis with polyangiitis: a report of three cases.

BACKGROUND: Granulomatosis with polyangiitis (GPA) is characterized by necrotizing granulomatous inflammation with necrotizing vasculitis predominantly affecting small to medium vessels. The survival rates have drastically improved; however, GPA can be lethal, with older patients having a worse prognosis and higher mortality than younger patients. Moreover, the incidence of various cancers has been reported to increase in patients with GPA. We aimed to discuss possible associations between GPA and lung cancer and emphasize the associated diagnostic challenges. CASE PRESENTATION: We encountered three older patients with chronic GPA who developed lung cancer during long-term follow-up. Two of the patients had a smoking history, with one having silicosis and the other having chronic obstructive pulmonary disease. Furthermore, all of them had radiation exposure from repeated radiography/computed tomography. All the patients had confirmed GPA, and vasculitis relapse was first suspected when new lung lesions were noted during follow-up. However, they had no new clinical symptoms, and serum ANCA titer increased only in one patient. All the patients received standard immunosuppressive treatment but eventually died. CONCLUSIONS: Lung cancer is uncommon in patients with GPA; however, the similarity between the imaging findings of lung cancer and GPA may pose a diagnostic challenge. Clinicians should be particularly vigilant when treating older patients with an increased risk of cancer, as they are often asymptomatic or have poorly apparent clinical features.

Lung adenocarcinoma discovered during the follow-up of lung-dominant connective tissue disease: a case report and literature review.

Interstitial lung disease (ILD) can lead to lung cancer, which brings great challenges to differential diagnosis and comprehensive treatment. However, the clinical features of lung-dominant connective tissue disease (LD-CTD) related ILD combined with lung cancer has not been validated. We report the case of an 80-year-old woman with LD-CTD treated regularly with nintedanib who presented progressive dyspnoea and hypoxemia after recurrent viral infections. Her chest computed tomography (CT) showed aggravated interstitial fibrosis in both lower lungs with moderate right pleural effusion. Clinicians should be alert to lung cancer in patients who are experiencing poor responsiveness to treatment or acute progression of ILD. The available literatures about the differential diagnosis of clinical manifestations, imaging, treatment and prognosis of LD-CTD are reviewed and discussed in this study.

A pulmonary artery was embolized in a patient with an occluded pulmonary vein to manage massive hemoptysis.

BACKGROUND: Stenosis and obliteration of the pulmonary vein can be developed by multiple diseases and might cause hemoptysis. Traditional therapy including surgical procedure and conservative treatments might be inappropriate choices to manage massive hemoptysis. CASE PRESENTATION: A 64-year-old man, diagnosed with advanced stage IVA lung squamous cell carcinoma, presented with dyspnea and recurrent, massive hemoptysis. An initial contrast-enhanced computed tomography revealed a giant tumor in the left lung hilus and occlusion of the left superior pulmonary vein. Despite immediate selective bronchial artery embolization and simultaneous embolization of an anomalous branch of the internal thoracic artery, the massive hemoptysis continued. Subsequently, embolization of the left superior pulmonary artery was performed, achieving functional pulmonary lobectomy, which successfully treated the hemoptysis without relapse during a six-month follow-up. The patient continues to undergo cancer therapy and remains stable. CONCLUSIONS: This case successfully managed massive hemoptysis associated with lung cancer invasion into the pulmonary vein through functional pulmonary lobectomy via embolization of the corresponding pulmonary artery.

The associates of anxiety among lung cancer patients: Dehydroepiandrosterone (DHEA) as a potential biomarker.

OBJECTIVE: Anxiety is a prevalent comorbidity in lung cancer (LC) patients associated with a decline in quality of life. Dehydroepiandrosterone (DHEA), a neuroactive steroid, levels rise in response to stress. Prior research on the association between DHEA and anxiety has yielded contradictory results and no study has investigated this association in LC patients. METHODS: A total of 213 patients with LC were recruited from a general hospital. Data on demographic and cancer-related variables were collected. Using the Chinese version of the Hospital Anxiety and Depression Scale (HADS), the degree of anxiety was determined. Cortisol, DHEA, and Dehydroepiandrosterone sulfate (DHEA-S) levels in saliva were measured. Adjusting for confounding variables, a multivariate regression analysis was conducted. RESULTS: 147 men and 66 women comprised our group with an average age of 63.75 years. After accounting for demographic and treatment-related factors, anxiety levels were significantly correlated with, post-traumatic stress symptoms (PTSSs) (ß = 0.332, p < 0.001) and fatigue (ß = 0.247, p = 0.02). Association between anxiety and three factors, including DHEA, PTSSs, and fatigue, was observed in patients with advanced cancer stages (III and IV) (DHEA ß = 0.319, p = 0.004; PTSS ß = 0.396, p = 0.001; fatigue ß = 0.289, p = 0.027) and those undergoing chemotherapy (DHEA ß = 0.346, p = 0.001; PTSS ß = 0.407, p = 0.001; fatigue ß = 0.326, p = 0.011). CONCLUSIONS: The association between anxiety and DHEA remained positive in advanced cancer stages and chemotherapy patients. Further study is necessary to determine whether DHEA is a potential biomarker of anxiety in LC patients.

Risk factors for interstitial lung disease in patients with non-small cell lung cancer with epidermal growth factor receptor-tyrosine kinase inhibitors: A systematic review and meta-analysis.

BACKGROUND: The use of epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) can potentially result in interstitial lung disease (ILD), which can substantially impact a patient's quality of life, subsequently leading to the interruption or discontinuation of EGRF-TKI treatment. Clinicians, therefore, need to thoroughly assess patients to determine if they are at risk for ILD. METHODS: We searched for observational study in the following databases: MEDLINE via the PubMed, CENTRAL, and IchushiWeb. The primary outcome was risk factors for the development of ILD, while the secondary outcome was risk factors for the severity of ILD. Of the 1602 studies returned, we selected 11 for meta-analysis, performed using a random-effects model. RESULTS: Risk factors for developing ILD were sex (odds ratio (OR), 1.87; 95% confidence interval (CI), 1.08-3.22; I2 = 0%; P = 0.02), smoking history (OR, 2.13; 95% CI, 1.51-3.00; I2 = 3 4%; P = 0.0001), and history of ILD (OR = 5.95; 95% CI, 3.34-10.59; I2 = 67%; P = 0.0009). Age, previous thoracic surgery or radiotherapy, performance status, histological type of lung cancer, and treatment line were not statistically significant risk factors for ILD. Risk factors identified in one study were serum albumin level, history of nivolumab use, radiographic residual lung volume, and history of pulmonary infection. CONCLUSIONS: We identified risk factors for developing ILD in patients with non-small cell lung cancer treated with EGFR-TKIs.

Pembrolizumab-associated anti-MDA5 dermatomyositis in a patient with lung cancer: a first case report.

We report the first case of anti-melanoma differentiation-associated gene 5 (MDA5)-positive dermatomyositis as a systemic immune-related adverse event in a 64-year-old man receiving pembrolizumab to treat advanced lung cancer. The patient experienced hypothyroidism, myalgia, skin involvement, dyspnoea and diarrhoea. Laboratory tests revealed raised inflammatory markers, hypercreatinekinasemia and anti-MDA5 autoantibodies. Electroneuromyography and pathognomonic signs on physical examination confirmed the diagnosis of pauci-myopathic dermatomyositis. Pembrolizumab was discontinued and immunosuppressive therapy led to rapid and progressive improvement, with complete remission of dermatomyositis. This case report widens the spectrum of systemic immune-related adverse events associated with pembrolizumab.

Analysis of related factors of CRA in lung cancer patients with different serum iron levels: A retrospective cohort study.

BACKGROUND: Serum iron, an essential component of hemoglobin (Hb) synthesis in vivo, is a crucial parameter for evaluating the body's iron storage and metabolism capacity. Iron deficiency leads to reduced Hb synthesis in red blood cells and smaller red blood cell volume, ultimately resulting in iron-deficiency anemia. Although serum iron cannot independently evaluate iron storage or metabolism ability, it can reflect iron concentration in vivo and serve as a good predictor of iron-deficiency anemia. Therefore, exploring the influence of different serum iron levels on anemia and diagnosing and treating iron deficiency in the early stages is of great significance for patients with lung cancer. AIM: This study aims to explore the related factors of cancer-related anemia (CRA) in lung cancer and construct a nomogram prediction model to evaluate the risk of CRA in patients with different serum iron levels. METHODS: A single-center retrospective cohort study was conducted, including 1610 patients with lung cancer, of whom 1040 had CRA. The relationship between CRA and its influencing factors was analyzed using multiple linear regression models. Lung cancer patients were divided into two groups according to their serum iron levels: decreased serum iron and normal serum iron. Each group was randomly divided into a training cohort and a validation cohort at a ratio of 7:3. The influencing factors were screened by univariate and multivariate logistic regression analyses, and nomogram models were constructed. The area under the receiver operating characteristic (ROC) curve, calibration curve, and decision curve analysis (DCA) were used to evaluate the models. RESULTS: CRA in lung cancer is mainly related to surgery, chemotherapy, Karnofsky Performance Status (KPS) score, serum iron, C-reactive protein (CRP), albumin, and total cholesterol (p < 0.05). CRA in lung cancer patients with decreased serum iron is primarily associated with albumin, age, and cancer staging, while CRA in lung cancer patients with normal serum iron is mainly related to CRP, albumin, total cholesterol, and cancer staging. The area under the ROC curve of the training cohort and validation cohort for the prediction model of lung cancer patients with decreased serum iron was 0.758 and 0.760, respectively. Similarly, the area under the ROC curve of the training cohort and validation cohort for the prediction model of lung cancer patients with normal serum iron was 0.715 and 0.730, respectively. The calibration curves of both prediction models were around the ideal 45° line, suggesting good discrimination and calibration. DCA showed that the nomograms had good clinical utility. CONCLUSION: Both models have good reliability and validity and have significant clinical value. They can help doctors better assess the risk of developing CRA in lung cancer patients. CRP is a risk factor for CRA in lung cancer patients with normal serum iron but not in patients with decreased serum iron. Therefore, whether CRP and the inflammatory state represented by CRP will further aggravate the decrease in serum iron levels, thus contributing to anemia, warrants further study.

Impact of Anti-angiogenic Drugs on Severity of COVID-19 in Patients with Non-Small Cell Lung Cancer.

Introduction: The 2019 coronavirus disease (COVID-19) pandemic has reshaped oncology practice, but the impact of anti-angiogenic drugs on the severity of COVID-19 in patients with non-small cell lung cancer (NSCLC) remains unclear. Patients and Methods: We carried out a retrospective study involving 166 consecutive patients with NSCLC who were positive for COVID-19, aiming to determine the effects of anti-angiogenic drugs on disease severity, as defined by severe/critical symptoms, intensive care unit (ICU) admission/intubation, and mortality outcomes. Risk factors were identified using univariate and multivariate logistic regression models. Results: Of the participants, 73 had been administered anti-angiogenic drugs (termed the anti-angiogenic therapy (AT) group), while 93 had not (non-AT group). Comparative analyses showed no significant disparity in the rates of severe/critical symptoms (21.9% vs 35.5%, P = 0.057), ICU admission/intubation (6.8% vs 7.5%, P = 0.867), or death (11.0% vs 9.7%, P = 0.787) between these two groups. However, elevated risk factors for worse outcomes included age ≥ 60 (odds ratio (OR): 2.52, 95% confidence interval (CI): 1.07-5.92), Eastern Cooperative Oncology Group performance status of 2 or higher (OR: 21.29, 95% CI: 4.98-91.01), chronic obstructive pulmonary disease (OR: 7.25, 95% CI: 1.65-31.81), hypertension (OR: 2.98, 95% CI: 1.20-7.39), and use of immunoglobulin (OR: 5.26, 95% CI: 1.06-26.25). Conclusion: Our data suggests that the use of anti-angiogenic drugs may not exacerbate COVID-19 severity in NSCLC patients, indicating their potential safe application even during the pandemic period.

Treatment of malignant airway obstruction with Y-shape sigma stent loaded with I125 seeds installed via rigid bronchoscopy.

PURPOSE: To summarize and analyze the safety and efficacy of a Y-shape Sigma stent loaded with I125 in patients with inoperable malignant main airway obstruction. METHODS: This study was approved by the Institutional Ethics Committee, and a written informed consent was obtained from each participant. A Y-shape Sigma stent loaded with I125 was placed under vision from rigid bronchoscopy. The primary endpoint was alleviation of symptoms and improvement of Karnofsky Performance Status (KPS) score, and the secondary endpoint was complications and technical success. RESULTS: From November 2018 through June 2023, total 33 patients with malignant airway obstruction were palliatively treated by installing Y-shape Sigma stents loaded with I125. The airway lumen was immediately restored and the average airway opening significantly increased to 70 ± 9.4% after the procedure from baseline 30.2 ± 10.5% (p < 0.05). Average KPS score was improved from baseline 30.0 ± 10.0 to 70.0 ± 10.0 (p < 0.05) as well as PaO2 from baseline 50.1 ± 15.4 mmHg to 89.3 ± 8.6 mmHg (p < 0.05). The technical success rate of placing the stent in this study was 73%, and adverse events or complications including bleeding, I125 loss, and airway infection occurred during or after the procedure. CONCLUSION: Placement of Y-shape Sigma stents under vision from rigid bronchoscopy in the patients with malignant airway obstruction is feasible and it immediately alleviates dyspnea and significantly improves quality of life.

[Correlation Analysis between Neutrophil-to-lymphocyte Ratio 
and the Risk of Malnutrition in Stage IV Primary Lung Cancer].

BACKGROUND: Malnutrition is commonly associated with poor prognosis in patients with malignant tumors. The neutrophil-to-lymphocyte ratio (NLR) is an indicator of inflammation in the body and predicts the risk of malnutrition in a variety of diseases; however, its association with malnutrition in lung cancer patients is unclear. The aim of this study is to clarify the association between NLR and nutritional status in stage IV primary lung cancer and to further determine the optimal NLR cut-off that best predicts the risk of malnutrition. METHODS: A retrospective analysis of 209 patients admitted to the Department of Medical Oncology, Tianjin Medical University General Hospital with a primary diagnosis of stage IV lung cancer from May 2019 to February 2021 was performed, and the nutritional risk screening 2002 (NRS 2002) was used to examine their nutritional status. Patient demographic information, pathology, Karnofsky performance status (KPS) score, body mass index (BMI), comorbidities and clinical biochemical indicators were also included. The correlation between NLR and NRS 2002 was investigated. Receiver operating characteristic (ROC) curve was used to determine the best NLR cut-off predi cting malnutrition risk. Multivariable Logistic regression was used to assess the association between NLR and malnutrition risk. RESULTS: The rate of patients with stage IV primary lung cancer at nutritional risk was 36.36% (76/209). A significant positive correlation was observed between NLR values and NRS 2002 risk score (r=0.765, P<0.001). The ROC curve analysis indicated that an NLR of 3.94 was the optimal cut-off for predicting malnutrition risk (area under the curve=0.747, 95%CI: 0.678-0.815, P<0.001), which showed a sensitivity of 55%, a specificity of 86%, a positive predictive value of 68%, and a negative predictive value of 77%. Patients in the NLR>3.94 group had a significantly higher risk of malnutrition compared to those in the NLR≤3.94 group (69.49% vs 23.33%, P<0.001). Furthermore, NLR was identified as a risk factor for malnutrition in stage IV primary lung cancer patients. CONCLUSIONS: NLR is associated with the risk of malnutrition in stage IV primary lung cancer, and NLR can be used as one of the indicators for screening nutritional risk in patients with stage IV primary lung cancer.