Search Results (37)

Background/Objectives: Up to one third of pleural biopsies performed during medical thoracoscopy (MT) are labelled as non-specific pleuritis (NSP). The histological diagnosis of NSP has long been worrisome for pulmonologists, with the potential to evolve into a life-threatening condition. The aim of this study was to identify clinical and biological predictors for patients with a diagnosis of NSP to guide clinical decisions. Methods: Baseline, procedural and follow-up data of NSP patients were retrospectively analysed to identify potential outcome predictors. Results: Of the 272 patients who underwent MT, 192 (71%) were diagnosed with malignancies, 9 (3%) with benign diseases and 71 (26%) with NSP. At follow-up, 17% were diagnosed with malignant disease and 21% with a benign condition and 62% remained idiopathic. A thoracoscopist’s evaluation of the pleural appearance reported a PPV of 28% and an NPV of 91% to predict malignancy. Patients with a subsequent diagnosis of malignancy tended to have a higher volume of fluid drained than those with persistently idiopathic NSP [2.7 litres (L) vs. 1.6 L p = 0.06]. A lymphocytic pleural effusion was more common in the malignant and idiopathic groups (63% and 60%, respectively) than the benign group (16%; p = 0.06 and p = 0.01). The three groups had a similar rate of effusion recurrence. Overall survival was higher in patients with idiopathic pleural effusion than in those with malignant (p = 0.04) or benign disease (p = 0.008). Conclusions: NSP diagnosis hides a malignancy in one in five cases, underlying the importance of closely following up these patients. The volume of drained pleural fluid, cell count and thoracoscopist’s impression may guide clinicians in the challenging management of patients with NSP. Full article

Malignant mediastinal tumors are a group representing some of the most demanding oncological challenges for early, multi-level, and successful management. The timely identification of any suspicious clinical symptomatology is urgent in achieving an accurate, staged histological diagnosis, in order to follow up with an equally detailed medical therapeutic plan (interventional or not) and determine the principal goals regarding efficient overall treatment in these patients. We report a case of a 24-year-old male patient with an incident-free prior medical history. An initial chest X-ray was performed after the patient reported short-term, consistent moderate chest pain symptomatology, early work fatigue, and shortness of breath. The following imaging procedures (chest CT, PET-CT) indicated the presence of an anterior mediastinal mass (meas. ~11 cm × 10 cm × 13 cm, SUV: 8.7), applying additional pressure upon both right heart chambers. The Alpha-Fetoprotein (aFP) blood levels had exceeded at least 50 times their normal range. Two consecutive diagnostic attempts with non-specific histological results, a negative-for-malignancy fine-needle aspiration biopsy (FNA-biopsy), and an additional tumor biopsy, performed via mini anterior (R) thoracotomy with “suspicious” cellular gatherings, were performed elsewhere. After admission to our department, an (R) Video-Assisted Thoracic Surgery (VATS) was performed, along with multiple tumor biopsies and moderate pleural effusion drainage. The tumor’s measurements had increased to DMax: 16 cm × 9 cm × 13 cm, with a severe degree of atelectasis of the Right Lower Lobe parenchyma (RLL) and a pressure-displacement effect upon the Superior Vena Cava (SVC) and the (R) heart sinus, based on data from the preoperative chest MRA. The histological report indicated elements of a combined, non-seminomatous germ-cell mediastinal tumor, posthuberal-type teratoma, and embryonal carcinoma. The imminent chemotherapeutic plan included a “BEP” (Bleomycin^®/Cisplatin^®/Etoposide^®) scheme, which needed to be modified to a “VIP” (Cisplatin^®/Etoposide^®/Ifosfamide^®) scheme, due to an acute pulmonary embolism incident. While the aFP blood levels declined, even reaching normal measurements, the tumor’s size continued to increase significantly (DMax: 28 cm × 25 cm × 13 cm), with severe localized pressure effects, rapid weight loss, and a progressively worsening clinical status. Thus, an emergency surgical intervention took place via median sternotomy, extended with a complementary “T-Shaped” mini anterior (R) thoracotomy. A large, approx. 4 Kg mediastinal tumor was extracted, with additional RML and RUL “en-bloc” segmentectomy and partial mediastinal pleura decortication. The following histological results, apart from verifying the already-known posthuberal-type teratoma, indicated additional scattered small lesions of combined high-grade rabdomyosarcoma, chondrosarcoma, and osteosarcoma, as well as numerous high-grade glioblastoma cellular gatherings. No visible findings of the previously discovered non-seminomatous germ-cell and embryonal carcinoma elements were found. The patient’s postoperative status progressively improved, allowing therapeutic management to continue with six “TIP” (Cisplatin^®/Paclitaxel^®/Ifosfamide^®) sessions, currently under his regular “follow-up” from the oncological team. This report underlines the importance of early, accurate histological identification, combined with any necessary surgical intervention, diagnostic or therapeutic, as well as the appliance of any subsequent multimodality management plan. The diversity of mediastinal tumors, especially for young patients, leaves no place for complacency. Such rare examples may manifest, with equivalent, unpredictable evolution, obliging clinical physicians to stay constantly alert and not take anything for granted. Full article

Background/Objectives: Carbohydrate antigen 125 (CA125) is a glycoprotein commonly overexpressed in epithelial ovarian cancer and widely recognized as a tumor marker. However, elevated CA125 levels are also observed in various non-malignant conditions, including diseases affecting mucosal surfaces, pleural or peritoneal effusions, cirrhosis (with or without ascites), endometriosis, uterine fibroids, adenomyosis, pelvic inflammatory disease, and pregnancy. This review aims to explore the role of CA125 in non-malignant serous effusions, highlighting its diagnostic and prognostic potential beyond the realm of oncology. Methods: A comprehensive literature search was conducted across multiple databases and clinical trial registries. Eligible studies included full-text original research articles, reviews, and case reports published in English over the past 10 years. Inclusion criteria were limited to studies involving human subjects and focused on the role of CA125 in non-malignant serous effusions. Results: CA125 is produced by coelomic epithelial cells lining the ovary, pleura, pericardium, and peritoneum. Its serum concentration is not significantly influenced by age, body weight, or renal function, even in the advanced stages of the disease. In peritoneal conditions, CA125 is synthesized by mesothelial cells and serves as a potential marker of peritoneal involvement. The prevailing pathophysiological mechanism suggests that mechanical stretching of mesothelial cells due to ascitic pressure stimulates CA125 release. Similarly, in heart failure, mesothelial cells of the pericardium produce CA125, which correlates with congestion severity, supports risk stratification, and may inform diuretic therapy. Conclusions: While a threshold of 35 U/mL is established for malignancy, no standardized cutoff exists for CA125 in non-malignant conditions. The utility of CA125 measurement in peritoneal, pleural, or pericardial effusions—and cardiovascular diseases such as acute heart failure—for purposes of differential diagnosis, treatment guidance, or prognostication warrants further investigation through prospective clinical trials. Full article

Pleural carcinomatosis (PC) and malignant pleural effusion (MPE) affect up to 20% of patients with non-small cell lung cancer (NSCLC) and are usually synonymous with poor prognosis. Pressurized Intra-Thoracic Aerosol Chemotherapy (PITAC) is a novel and promising technique to control MPE in PC-NSCLC. This pilot study aimed to assess the feasibility, safety, and efficacy of PITAC in terms of palliative pleurodesis and evaluate the local antineoplastic control by analyzing patient-derived primary cell cultures. From January to December 2023, seven patients underwent PITAC with tailored doses of cisplatin and doxorubicin. There were four males and three females, with a median age of 65 (IQR:19) years. No operating room contamination by aerosolized chemotherapeutics was observed. No intraoperative complications occurred, and 30-day mortality was nil. One patient developed a postoperative prolonged air leak. The median chest tube stay was 2 (IQR:2) days, and the median hospital stay was 4 (IQR:2) days. No systemic toxicity nor hypersensitivity to chemotherapeutics were observed. All patients developed effective pleurodesis in 30 days. Cell cultures obtained from biopsy of PC-NSCLC sampled before PITAC formed confluent and monolayer sheets of attached tumor cells, while after 30 min from PITAC, cultures exhibited a significant reduction in the cancer cells’ growth. Effective pleurodesis was observed three and six months after surgery in all patients. PITAC is a safe and effective technique to control MPE recurrence and might revolutionize loco-regional therapy for PC-NSCLC. Further research should assess its oncological role. Full article

Non-expandable lung (NEL) occurs when the lung fails to fully re-expand after pleural fluid drainage, complicating management and limiting therapeutic options. Diagnosis, based on clinical symptoms, pleural manometry, and traditional imaging, is often delayed to the peri- or post-procedural stages, leading to improper management, complications, and higher healthcare costs. Therefore, early, pre-procedural diagnostic methods are needed. Thoracic ultrasound (TUS) has emerged as a non-invasive tool with the potential to enhance diagnostic accuracy and guide clinical decisions, yet, it remains inadequately studied within the context of NEL. We conducted a non-systematic narrative review using a structured methodology, including a comprehensive database search, predefined inclusion criteria, and QUADAS-2 quality assessment. This approach ensured a rigorous synthesis of evidence on TUS in NEL, with the aim of identifying knowledge gaps and guiding future studies. Non-invasive, real-time, bedside M-mode TUS has demonstrated efficacy in predicting NEL prior to thoracentesis by detecting an absent sinusoidal sign and reduced atelectatic lung movement. Emerging experimental techniques, including 2D shear wave elastography (SWE), speckle tracking imaging (STI) strain analysis, the lung/liver echogenicity (LLE) ratio, TUS assessment of dynamic air bronchograms, and pleural thickening evaluation, show additional potential to enhance pre-procedural NEL detection. However, all these methods have significant limitations that require further comprehensive investigation. Despite their significant promise, TUS modalities for early NEL detection still require rigorous validation and standardization before broad clinical use. A multimodal diagnostic approach, combining clinical manifestations, pleural manometry, radiologic and ultrasonographic findings, along with emerging techniques (once fully validated), may provide the most extensive framework for NEL. Regardless of advancements, patient-centered care and shared decision-making remain essential. Further research is needed to improve outcomes, reduce healthcare costs, and enhance long-term treatment strategies. Full article

Background and Objectives: Non-malignant pleural effusions (NMPEs) are the most frequently encountered pleural disease. They arise from various non-malignant, non-infectious clinical conditions, including cardiac, renal, and hepatic organ dysfunction. Despite their wide prevalence, there is a lack of literature for NMPE. This publication aims to provide an updated overview of the causes, diagnostic strategies, and management options for NMPE. Materials and Methods: This review synthesizes findings from studies published on NMPE, focusing on the presentation, diagnosis (such as imaging and pleural fluid analysis), and management strategies. Studies were selected based on relevance and were analyzed to provide a comprehensive summary of current practices. Results: The review highlights different etiologies of NMPE, including organ-specific factors. Imaging, pleural fluid analysis, and clinical correlation remain crucial in diagnosing the etiology of NMPE. Treatment strategies are largely dependent on the underlying condition. Medical management remains the mainstay for many causes. In some cases, interventions, such as thoracentesis, tunneled indwelling pleural catheter, or pleurodesis, are necessary. Conclusions: NMPE is a heterogeneous condition with a wide prevalence and significant implications. They present a diagnostic and management challenge due to patient complexity and evolving therapeutic options. Full article

Background/Objectives: Malignant pleural effusions (MPEs) pose a significant challenge in clinical practice and exert a considerable socio-economic burden on the healthcare system, affecting approximately 1 million individuals annually. These effusions are a leading cause of debilitating dyspnea and a diminished quality of life among cancer patients, with distant metastasis to the pleural layers occurring in about 20% of cases during treatment. Methods: A cross-sectional, observational case-control study was conducted on 151 Bulgarian patients with a hydrothorax. The control group included 72 patients with benign diseases, confirmed via biopsy, with 38 having inflammatory and 34 non-inflammatory pleural effusions. The other 79 patients had malignant pleural involvement. These groups are representative of the main types of pleural pathology. Results: The study found that all of the tumor markers, except for PIVKA-II (Protein induced by vitamin K absence-II), showed statistically significant differences between the malignant and non-malignant patient groups, with CAE (carcinoembryonic antigen) and CA19-9 showing the most notable differences. The Receiver Operating Characteristic (ROC) analysis revealed that CA72-4 had the best ability to distinguish between the two groups, while PIVKA was the weakest, with optimal cut-off values for all of the relevant tumor markers being derived using the Youden index. Conclusions: In conclusion, our study highlights the transformative potential of pleural fluid tumor markers as precise and minimally invasive resources for distinguishing malignant from non-malignant pleural effusions. These findings pave the way for improved diagnostic accuracy and personalized clinical management, addressing a critical gap in the care of patients with pleural pathologies. Full article

Background and Objectives: The diversity of patients with malignant pleural effusion (MPE) due to non-small cell lung cancer (NSCLC) as well as the variability in mutations makes it essential to improve molecular characterization. Objective: Describe clinical, pathological, and molecular characteristics MPE in a Caucasian population. Materials and Methods: Retrospective study of patients with NSCLC diagnosis who had undergone a molecular study from 1 January 2018–31 December 2022. Univariate analysis was performed to compare patient characteristics between the group with and without MPE and molecular biomarkers. Results: A total of 400 patients were included; 53% presented any biomarker and 29% had MPE.PDL1, which was the most frequent. EGFR mutation was associated with women (OR:3.873) and lack of smoking (OR:5.105), but not with MPE. Patients with pleural effusion were older and had lower ECOG. There was no significant difference in the presence of any biomarker. We also did not find an association between the presence of specific mutations and MPE (22.4% vs. 18%, p = 0.2), or PDL1 expression (31.9% vs. 35.9%, p = 0.3). Being younger constituted a protective factor for the presence of MPE (OR:0.962; 95% CI 0.939–0.985, p = 0.002), as well as ECOG ≤ 1 (OR:0.539; 95% CI 0.322–0.902, p = 0.01). Conclusions: This is the first study that describes the clinical, pathological, and molecular characteristics of MPE patients due to NSCLC in a Caucasian population. Although overall we did not find significant differences in the molecular profile between patients with MPE and without effusion, EGFR mutation was associated with a tendency towards pleural progression. Full article

Thoracostomy and chest tube placement are key procedures in treating pleural diseases involving the accumulation of fluids (e.g., malignant effusions, serous fluid, pus, or blood) or air (pneumothorax) in the pleural cavity. Initially described by Hippocrates and refined through the centuries, chest drainage achieved a historical milestone in the 19th century with the creation of closed drainage systems to prevent the entry of air into the pleural space and reduce infection risk. The introduction of plastic materials and the Heimlich valve further revolutionized chest tube design and function. Technological advancements led to the availability of various chest tube designs (straight, angled, and pig-tail) and drainage systems, including PVC and silicone tubes with radiopaque stripes for better radiological visualization. Modern chest drainage units can incorporate smart digital systems that monitor and graphically report pleural pressure and evacuated fluid/air, improving patient outcomes. Suction application via wall systems or portable digital devices enhances drainage efficacy, although careful regulation is needed to avoid complications such as re-expansion pulmonary edema or prolonged air leak. To prevent recurrent effusion, particularly due to malignancy, pleurodesis agents can be applied through the chest tube. In cases of non-expandable lung, maintaining a long-term chest drain may be the most appropriate approach and procedures such as the placement of an indwelling pleural catheter can significantly improve quality of life. Continued innovations and rigorous training ensure that chest tube insertion remains a cornerstone of effective pleural disease management. This review provides a comprehensive overview of the historical evolution and modern advancements in pleural drainage. By addressing both current technologies and procedural outcomes, it serves as a valuable resource for healthcare professionals aiming to optimize pleural disease management and patient care. Full article

Malignant pleural effusion (MPE) from patients with advanced non-small-cell lung cancer (NSCLC) has been proven valuable for molecular analysis; however, simultaneous detection of driver fusions in MPE is still challenging. In this study, we investigated the Idylla™ GeneFusion Panel, a stand-alone test in tissue samples, in the evaluation of ALK, ROS1, RET and MET ex14 skipping mutations in MPE and compared its performance with routine reference methods (Real-time-based and Next-generation Sequencing—NGS). The inclusion criteria for sample selection were as follows: advanced NSCLC harboring ALK, ROS1, RET fusions or MET exon-skipping alterations and the availability of MPE collected at diagnosis or disease progression. Molecular alterations have been investigated on tissue by fluorescence in situ hybridization (FISH) or Real-time PCR or NGS. For molecular profiling with the Idylla™ GeneFusion, 200 µL of MPE supernatants combined with 50 µL of RNA Later solution were loaded into the Idylla™ cartridge without cfRNA extraction. The Idylla™ GeneFusion Assay performed on MPEs was able to confirm molecular profile, previously diagnosed with conventional methods, in all cases. Our data confirm that MPE are suitable material for investigating fusion alterations. The Idylla™ GeneFusion, although indicated for investigation of tissue samples, offers the possibility of performing a molecular characterization of supernatants without undertaking the entire cfRNA extraction procedure providing a rapid and reliable strategy for the detection of actionable genetic alterations. Full article

Background: Malignant pleural effusion (MPE) affects up to 15% of patients with malignancy, and the prevalence is increasing. Non-expandable lung (NEL) complicates MPE in up to 30% of cases. However, it is not known if patients with malignant pleural effusion and NEL are more symptomatic in activities of daily living compared to patients with MPE with expandable lung. Methods: This was an observational study on consecutively recruited patients with MPE from our pleural clinic. Before thoracentesis, patients completed patient-reported outcomes on cancer symptoms (ESAS), health-related quality of life (5Q-5D-5L), and dyspnoea scores. Following thoracentesis, patients scored dyspnoea relief and symptoms during thoracentesis. Data on focused lung ultrasound and pleural effusion biochemistry were collected. The non-expandable lung diagnosis was made by pleural experts based on radiological and clinical information. Results: We recruited 43 patients, including 12 with NEL (28%). The NEL cohort resembled those from previous studies concerning ultrasonography, pleural fluid biochemistry, and fewer cases with high volume thoracentesis. Patients with and without NEL were comparable concerning baseline demography. The 5Q-5D-5L utility scores were 0.836 (0.691–0.906) and 0.806 (0.409–0.866), respectively, for patients with and without NEL. We observed no between-group differences in symptom burden or health-related quality of life. Conclusion: While the presence of NEL affects the clinical management of recurrent MPE, the presence of NEL seems not to affect patients’ overall symptom burden in patients with MPE. Full article

Background: Spheroids generated by tumor cells collected from malignant pleural effusion (MPE) were shown to retain the characteristics of the original tumors. This ex vivo model might be used to predict the response of non-small cell lung cancer (NSCLC) to anticancer treatments. Methods: The characteristics, epidermal growth factor receptor (EGFR) mutation status, and clinical response to EGFR-TKIs treatment of enrolled patients were recorded. The viability of the spheroids generated from MPE of enrolled patients were evaluated by visualization of the formazan product of the MTT assay. Results: Spheroids were generated from 14 patients with NSCLC-related MPE. Patients with EGFR L861Q, L858R, or Exon 19 deletion all received EGFR-TKIs, and five of these seven patients responded to treatment. The viability of the spheroids generated from MPE of these five patients who responded to EGFR-TKIs treatment was significantly reduced after gefitinib treatment. On the other hand, gefitinib treatment did not reduce the viability of the spheroids generated from MPE of patients with EGFR wild type, Exon 20 insertion, or patients with sensitive EGFR mutation but did not respond to EGFR-TKIs treatment. Conclusion: Multicellular spheroids generated from NSCLC-related MPE might be used to predict the response of NSCLC to treatment. Full article

Objective: This study aimed to investigate the optimal volume of serous fluid needed for accurate diagnosis using The International System for Reporting Serous Fluid Cytopathology (TIS), as well as to provide information on the distribution of serous effusion cases in the TIS categories (ND: non-diagnostic, NFM: negative for malignancy, AUS: atypia of undetermined significance, SFM: suspicious for malignancy, MAL: malignant) and relevant epidemiological data. Methods: A retrospective analysis of 2340 serous effusion cases (pleural, peritoneal, and pericardial) from two hospitals between 2018 and 2020 was conducted. TIS categories were assigned to each case, and for 1181 cases, these were correlated with the volume of the analyzed fluid. Results: Our study found statistically significant differences in volume distributions between certain TIS categories. Statistically lower volumes were observed in NFM compared to MAL, in UNCERTAIN (ND, AUS, SFM) compared to both MAL and NFM, and in NOT MAL (ND, NFM, AUS, SFM) compared to MAL. However, these differences were not substantial enough to hold any clinical relevance. Conclusions: This study suggests that while fluid volume may slightly influence the TIS category, it does not impact the diagnostic accuracy of serous effusion cytology. Therefore, the ideal serous effusion specimen volume can be defined solely by practical parameters. Full article

Background: Non-expandable lung (NEL) has severe implications for patient symptoms and impaired lung function, as well as crucial implications for the management of malignant pleural effusion (MPE). Indwelling pleural catheters have shown good symptom relief for patients with NEL; hence, identifying patients early in their disease is vital. With the inability of the lung to achieve pleural apposition following thoracentesis and the formation of a hydropneumothorax, traditionally, chest X-ray and clinical symptoms have been used to make the diagnosis following thoracentesis. It is our aim to investigate whether ultrasound measurement of lung movement during respiration can predict NEL before thoracentesis, thereby aiding clinicians in their planning for the optimal treatment of affected patients. Methods: A total of 49 patients were consecutively included in a single-centre trial performed at a pleural clinic. Patients underwent protocolled ultrasound assessment pre-thoracentesis with measurements of lung and diaphragm movement and shear wave elastography measurements of the pleura and pleural effusion at the planned site of thoracentesis. Results: M-mode measurements of lung movement provided the best diagnostic ROC-curve results, with an AUC of 0.81. Internal validity showed good results utilising the calibration belt test and Brier test. Conclusion: M-mode measurement of lung movement shows promise in diagnosing NEL before thoracentesis in patients with known or suspected MPE. A validation cohort is needed to confirm the results. Full article

Objectives: The primary aim of this study was to improve the diagnosis of lymphocytic pleural effusions (LPEs) by combining their ultrasound characteristics with their macroscopic and biochemical features. Methods: This prospective, single-center, clinical observational study was conducted over a period of three years. The possible malignant etiology of LPEs was assessed using several diagnostic criteria: 1. ultrasound characteristics of the LPEs; 2. typical combinations of macroscopic and ultrasound features; and 3. the logistic regression method with three parameters—pleural nodularity, absence of fibrin, and serum protein concentration. Results: Eighty-four patients with LPEs were included in this study. Pleural nodularity (first criterion) was an ultrasound characteristic that yielded the best individual results (p < 0.001) in the differentiation of malignant and nonmalignant etiologies of LPEs (accuracy 73.81%). The combination of the second and third criteria yielded the best results in the prediction of a malignant etiology of LPEs (sensitivity 90.48%, specificity 83.33%, PPV 84.44%, NPV 89.74%, accuracy 86.90%). Based on the results of this prospective study, a protocol for the diagnostic procedure of lymphocytic pleural effusions without a definitive fluid diagnosis has been proposed. Conclusions: A combination of the ultrasound characteristics of LPEs and their macroscopic and biochemical features has improved the predictive accuracy for the malignant etiology of LPEs. Full article