A systematic review of patient-derived tumor organoids generation from malignant effusions.

This review assesses the possibility of utilizing malignant effusions (MEs) for generating patient-derived tumor organoids (PDTOs). Obtained through minimally invasive procedures MEs broaden the spectrum of organoid sources beyond resection specimens and tissue biopsies. A systematic search yielded 11 articles, detailing the successful generation of 190 ME-PDTOs (122 pleural effusions, 54 malignant ascites). Success rates ranged from 33% to 100%, with an average of 84% and median of 92%. A broad and easily applicable array of techniques can be employed, encompassing diverse collection methods, variable centrifugation speeds, and the inclusion of approaches like RBC lysis buffer or centrifuged ME supernatants supplementation, enhancing the versatility and accessibility of the methodology. ME-PDTOs were found to recapitulate primary tumor characteristics and were primarily used for drug screening applications. Thus, MEs are a reliable source for developing PDTOs, emphasizing the need for further research to maximize their potential, validate usage, and refine culturing processes.

Innovative Invasive Loco-Regional Techniques for the Treatment of Lung Cancer.

Surgical resection is still the standard treatment for early-stage lung cancer. A multimodal treatment consisting of chemotherapy, radiotherapy and/or immunotherapy is advised for more advanced disease stages (stages IIb, III and IV). The role of surgery in these stages is limited to very specific indications. Regional treatment techniques are being introduced at a high speed because of improved technology and their possible advantages over traditional surgery. This review includes an overview of established and promising innovative invasive loco-regional techniques stratified based on the route of administration, including endobronchial, endovascular and transthoracic routes, a discussion of the results for each method, and an overview of their implementation and effectiveness.

Good's syndrome and COVID-19: case report and literature review.

Background: Good's syndrome (GS) is an adult-onset acquired immunodeficiency, in which patients present with thymoma and hypogammaglobulinemia (HGG). GS is characterized by low to absent peripheral B cells and impaired T-cell mediated immunity, often resulting in various (opportunistic) infections and concurrent autoimmune disorders. In this case report, we present a case of a patient with GS and coronavirus disease 2019 (COVID-19) infection after surgical removal of a thymoma. The simultaneous occurence of these two entities is extremely rare. Case Description: A 55-year-old man presented with oral lichen planus and cutaneous lesions. Additional symptoms included a weight loss of 5 kilograms in the last six months. Computed tomography (CT) and positron emission tomography (PET) of the chest showed a large anterior mediastinal mass with a maximum diameter of 10 centimetres. A core needle biopsy was performed, which led to a pathological diagnosis of thymoma type AB. In addition to these earlier findings, laboratory analysis revealed HGG. The combination of a thymoma and HGG led to a diagnosis of GS. Induction chemotherapy with cisplatin-etoposide was started, however, the patient developed COVID-19 after 2 cycles. Treatment with remdesivir was initiated and, subsequently, a thymectomy via sternotomy was performed. Final pathology confirmed a thymoma type AB of 14 centimetres, fully encapsulated, and without invasion. Resection margins were negative and the tumour was classified as pT1aN0, R0 resection. The patient has received immunoglobulin treatments every 4 weeks for his GS and has not developed any new infections since the start of this therapy. Conclusions: Patients with GS are prone to developing (pulmonary) infections. Clinicians should be aware of the possible clinical effects of COVID-19 infections in this patient population.

New Implications of Patients' Sex in Today's Lung Cancer Management.

This paper describes where and how sex matters in today's management of lung cancer. We consecutively describe the differences between males and females in lung cancer demographics; sex-based differences in the immune system (including the poorer outcomes in women who are treated with immunotherapy but no chemotherapy); the presence of oncogenic drivers and the response to targeted therapies according to sex; the greater benefit women derive from lung cancer screening and why they get screened less; and finally, the barriers to smoking cessation that women experience. We conclude that sex is an important but often overlooked factor in modern-day thoracic oncology practice.

Evaluation of Cytologic Sample Preparations for Compatibility With Nucleic Acid Analysis.

OBJECTIVES: In this study, the influence of several key elements of the cytologic sample workflow on DNA and RNA content was evaluated. METHODS: The A549 cell line, patient-derived organoids, and pleural effusions were used to investigate the effect of (1) several collection media and delayed time to processing; (2) cytology specimens; (3) cytologic staining; and (4) formalin-fixed, paraffin-embedded (FFPE) cell block processing on nucleic acid quality and quantity as determined by fragment analyzer, Qubit analysis (Thermo Fisher Scientific), and quantitative polymerase chain reaction-based analysis on the Idylla platform (Biocartis). RESULTS: Alcohol-based collection media (CytoRich Red [Thermo Fisher Scientific] and EtOH95%) displayed high DNA and RNA preservation capacity, while phosphate-buffered saline and, to a lesser extent, formalin were associated with high RNA quality. Cytospin and smear cytology specimens were subject to DNA and RNA loss. Cytologic staining had no further impact on sample quality, hence destaining is not necessary. Both H&E-stained and unstained FFPE sections are compatible with nucleic acid analysis, despite a strong decrease in DNA and RNA quality. CONCLUSIONS: Although several key elements of the cytologic sample workflow have an influence on DNA and RNA quality and quantity, the selection of these elements is also dependent on the downstream (ancillary) testing methods.

Polarization-sensitive optical coherence tomography in end-stage lung diseases: an ex vivo pilot study.

A non-invasive diagnostic tool to assess remodeling of the lung airways caused by disease is currently missing in the clinic. Measuring key features such as airway smooth muscle (ASM) thickness would increase the ability to improve diagnosis and enable treatment evaluation. In this research, polarization-sensitive optical coherence tomography (PS-OCT) has been used to image a total of 24 airways from two healthy lungs and four end-stage diseased lungs ex vivo, including fibrotic sarcoidosis, chronic obstructive pulmonary disease (COPD), fibrotic hypersensitivity pneumonitis, and cystic fibrosis. In the diseased lungs, except COPD, the amount of measured airway smooth muscle was increased. In COPD, airway smooth muscle could not be distinguished from surrounding collagen. COPD lungs showed increased alveolar size. 3D pullbacks in the same lumen provided reproducible assessment of airway smooth muscle (ASM). Image features such as thickened ASM and size/presence of alveoli were recognized in histology. The results of this study are preliminary and must be confirmed with further ex vivo and in vivo studies. PS-OCT is applicable for in vivo assessment of peribronchial and peribronchiolar lung structures and may become a valuable tool for diagnosis in pulmonology.

Comorbidities in Difficult-to-Control Asthma.

BACKGROUND: Difficult-to-control asthma is associated with significant medical and financial burden. Comorbidities are known to contribute to uncontrolled asthma. Better insight into the prevalence, nature, and risk factors of comorbidities may optimize treatment strategies in patients with difficult-to-control asthma and decrease disease burden. OBJECTIVES: The objectives of this study were to assess the prevalence, number, and type of comorbidities in difficult-to-control asthma compared with not-difficult-to-control asthma, and to investigate whether specific patient characteristics are associated with particular comorbidities. METHODS: A total of 5,002 adult patients with a prescription for high-dose (>1,000 µg) fluticasone or oral corticosteroids, extracted from 65 Dutch pharmacy databases, were sent questionnaires about patient characteristics. Of the 2,312 patients who returned the questionnaires, 914 were diagnosed with difficult-to-control asthma. Diagnoses of comorbidities (gastroesophageal reflux, nasal polyps, cardiovascular disease, anxiety/depression, obesity, and diabetes) were based on treatment prescriptions or questionnaires. Associations were assessed using multivariable logistic regression analyses. RESULTS: A total of 92% of patients with difficult-to-control asthma had ≥1 comorbidity. Patients with difficult-to-control asthma had more comorbidities (mean ± SD comorbidities 2.22 ± 1.27 vs 1.69 ± 1.32; P < .01), and a significantly higher prevalence of each comorbidity, compared with patients with not-difficult-to-control asthma, except for diabetes and nasal polyposis. Comorbidities were associated with specific patient characteristics, including older age, female gender, smoking history, and chronic prednisone use. CONCLUSIONS: Almost all patients with difficult-to-control asthma have comorbidities, in particular asthmatic women of older age, former smokers, and asthmatics who are prednisone dependent. Recognition of these typical characteristics can help physicians in the diagnostic workup, so that adequate preventive measures can be taken.

The prevalence of severe refractory asthma.

BACKGROUND: Severe asthma is characterized by difficulty to achieve disease control despite high-intensity treatment. However, prevalence figures of severe asthma are lacking, whereas longstanding estimates vary between 5% and 10% of all asthmatic patients. Knowing the exact prevalence of severe refractory asthma as opposed to difficult-to-control asthma is important for clinical decision making, drug development, and reimbursement policies by health authorities. OBJECTIVE: We sought to estimate the prevalence of severe refractory asthma as defined by the Innovative Medicine Initiative consensus. METHODS: Adult patients with a prescription for high-intensity treatment (high-dose inhaled corticosteroids and long-acting ß2-agonists or medium- to high-dose inhaled corticosteroids combined with oral corticosteroids and long-acting ß2-agonists) were extracted from 65 Dutch pharmacy databases, representing 3% of the population (500,500 inhabitants). Questionnaires were sent to 5,002 patients, of which 2,312 were analyzed. The diagnosis of asthma and degree of asthma control were derived from questionnaires to identify patients with difficult-to-control asthma. Inhalation technique was assessed in a random sample of 60 adherent patients (prescription filling, ≥80%). Patients with difficult-to-control asthma, adherence to treatment, and a correct inhalation technique were qualified as having severe refractory asthma. Results were mirrored to the Dutch population. RESULTS: Of asthmatic adults, 3.6% (95% CI, 3.0% to 4.1%) qualified for a diagnosis of severe refractory asthma, representing 10.4 patients per 10,000 inhabitants. CONCLUSION: The prevalence of severe refractory asthma might be lower than estimated by expert opinion. This implies that currently recognized severe asthma subphenotypes could meet the criteria of rare diseases.

Severe refractory asthma: an update.

Asthma is a heterogeneous disease in which adequate asthma control cannot be achieved in a substantial proportion despite currently available treatment possibilities. This subgroup has been defined as "severe refractory" asthma. Over the past years considerable progress has been made regarding a more exact definition of severe refractory asthma. A systematic approach to evaluate the asthma patient has been postulated. Further detailed classification into distinct phenotypes is ongoing to target the right treatment to the right patient. And, new therapeutic targeted treatment options are currently in development to provide possible new targets to improve disease state, symptoms and quality of life. This review will provide an update on the latest advancements with regard to all these domains.