Robotic Bronchoscopy in Lung Cancer Diagnosis.

BACKGROUND: The widespread use of chest CT has increased the number of detected pulmonary nodules. Nodules with intermediate risk of malignancy warrant further evaluation with PET-CT or sampling. Although sampling with conventional bronchoscopy presents lower complication rates compared to transthoracic needle biopsy (TTNB), it is limited by the inability to reach distal airways. To overcome this shortcoming, a new bronchoscopic technique named robotic bronchoscopy (RB) has emerged. METHODS: A literature review was used to clarify the rationale behind RB emergence, describe RB procedure, and summarize data regarding its efficacy and safety. RESULTS: The FDA has approved three RB platforms for clinical use. RB is safe, presenting a mortality and complication rate of 0% and 0-8.1%, respectively. Common complications include pneumothorax (0-5.7%) and minor bleeding (0-3.2%). However, its diagnostic yield remains lower than that of TTNB. CONCLUSIONS: RB is a promising bronchoscopic technique that aims to overcome the limitations of conventional bronchoscopy and improve upon the current techniques of guided bronchoscopy for the investigation of pulmonary nodules. Despite the lower complication rate, current evidence suggests a lower diagnostic yield compared to TTNB. Additional studies are required to adequately evaluate the role of RB in the diagnosis of pulmonary nodules.

Efficacy of NSCLC Rechallenge with Immune Checkpoint Inhibitors following Disease Progression or Relapse.

Immune checkpoint inhibitors (ICIs) are at the forefront of advanced non-small-cell lung cancer (NSCLC) treatment. Still, only 27-46% of patients respond to initial therapy with ICIs, and of those, up to 65% develop resistance within four years. After disease progression (PD), treatment options are limited, with 10% Objective Response Rate (ORR) to second or third-line chemotherapy. In this context, ICI rechallenge is an appealing option for NSCLC. Most data on the efficacy of ICI rechallenge are based on retrospective real-world studies of small, heavily pretreated, and heterogeneous patient groups. Despite these limitations, these studies suggest that ICI monotherapy rechallenge in unselected NSCLC patient populations who discontinued initial ICI due to PD is generally ineffective, with a median Progression-Free Survival (PFS) of 1.6-3.1 months and a Disease Control Rate (DCR) of 21.4-41.6%. However, there is a subpopulation that benefits from this strategy, and further characterization of this subgroup is essential. Furthermore, immunotherapy rechallenge in patients who discontinued initial immunotherapy following treatment protocol completion and progressed after an immunotherapy-free interval showed promising efficacy, with a DCR of 75-81%, according to post hoc analyses of several clinical trials. Future research on ICI rechallenge for NSCLC should focus on better patient stratification to reflect the underlying biology of immunotherapy resistance more accurately. In this review, we summarize evidence regarding rechallenge immunotherapy efficacy following NSCLC disease progression or relapse, as well as ongoing trials on immunotherapy rechallenge.

Medical treatment of pleural infection: antibiotic duration and corticosteroid usefulness.

The data about the optimal duration of antibiotics and the usefulness of corticosteroids in the management of parapneumonic effusion and pleural infection are scarce. Two randomised controlled trials evaluating short antibiotic courses (ODAPE and SLIM) and another trial assessing the benefit from corticosteroid use (STOPPE) in this setting were recently published. The aim of this journal club is to present these trials and discuss their significance and limitations. ODAPE compared the efficacy and safety of a short (2 weeks) versus an extended (3 weeks) course of amoxicillin-clavulanate in community-acquired complicated parapneumonic effusions, while SLIM compared the efficacy and safety of short (14-21 days) versus longer (28-42 days) antibiotic courses in patients with community- or hospital-acquired pleural infection. STOPPE assessed the benefit from dexamethasone use in patients with community-acquired pneumonia and concomitant pleural effusion. Both ODAPE and SLIM found that shorter antibiotic courses produce less adverse events while being equally efficacious to the longer courses in a subgroup of patients, such as those with pleural infection that is stabilised with only medical treatment and does not require surgery. In contrast, STOPPE found no benefit from the use of dexamethasone in unselected patients with pneumonia and pleural effusion. Due to the significant limitations of these trials, further studies are required to confirm these findings. Commentary on: Hassan M, et al. The Short versus Long Antibiotic Course for Pleural Infection Management (SLIM) randomised controlled open-label trial. ERJ Open Res 2023; 9: 00635-2022.Porcel JM, et al. Two vs. three weeks of treatment with amoxicillin-clavulanate for stabilized community-acquired complicated parapneumonic effusions. A preliminary non-inferiority, double-blind, randomized, controlled trial. Pleura Peritoneum 2020; 5: 20190027.Fitzgerald DB, et al. Steroid Therapy and Outcome of Parapneumonic Pleural Effusions (STOPPE): a pilot randomized clinical trial. Am J Respir Crit Care Med 2022; 205: 1093-1101.

Bacteriology, antibiotic resistance and risk stratification of patients with culture-positive, community-acquired pleural infection.

BACKGROUND: Community-acquired pleural infection (CAPI) is a growing health problem worldwide. Although most CAPI patients recover with antibiotics and pleural drainage, 20% require surgical intervention. The use of inappropriate antibiotics is a common cause of treatment failure. Awareness of the common causative bacteria along with their patterns of antibiotic resistance is critical in the selection of antibiotics in CAPI-patients. This study aimed to define CAPI bacteriology from the positive pleural fluid cultures, determine effective antibiotic regimens and investigate for associations between clinical features and risk for death or antibiotic-resistance, in order to advocate with more invasive techniques in the optimal timing. METHODS: We examined 158 patients with culture positive, CAPI collected both retrospectively (2012-2013) and prospectively (2014-2018). Culture-positive, CAPI patients hospitalized in six tertiary hospitals in Greece were prospectively recruited (N=113). Bacteriological data from retrospectively detected patients were also used (N=45). Logistic regression analysis was performed to identify clinical features related to mortality, presence of certain bacteria and antibiotic resistance. RESULTS: Streptococci, especially the non-pneumococcal ones, were the most common bacteria among the isolates, which were mostly sensitive to commonly used antibiotic combinations. RAPID score (i.e., clinical score for the stratification of mortality risk in patients with pleural infection; parameters: renal, age, purulence, infection source, and dietary factors), diabetes and CRP were independent predictors of mortality while several patient co-morbidities (e.g., diabetes, malignancy, chronic renal failure, etc.) were related to the presence of certain bacteria or antibiotic resistance. CONCLUSIONS: The dominance of streptococci among pleural fluid isolates from culture-positive, CAPI patients was demonstrated. Common antibiotic regimens were found highly effective in CAPI treatment. The predictive strength of RAPID score for CAPI mortality was confirmed while additional risk factors for mortality and antibiotic resistance were detected.

Drug resistance in patients with tuberculous pleural effusions.

PURPOSE OF REVIEW: To summarize data regarding categories, detection methods, prevalence and patterns of drug resistance among patients with tuberculous pleural effusion (TPE) and to comment on the management of suspected drug-resistant TPE. RECENT FINDINGS: Pleural and pulmonary tuberculosis (TB) present similar patterns of drug resistance. Approximately 10% and 6-10% of pleural Mycobacterium tuberculosis isolates are resistant to at least one first-line anti-TB drug or at least isoniazid, respectively. The prevalence of multidrug-resistant-pleural and extensively drug-resistant-pleural TB is 1-3% and 0-1%, respectively. SUMMARY: Although guidelines suggest the empirical standard anti-TB regimen (i.e. 2 months of isoniazid, rifampicin, pyrazinamide and ethambutol followed by 4 months of isoniazid and rifampicin) for TPE treatment, the data regarding drug resistance among TPE patients are limited. The few studies examining the issue report a notable drug resistance. In suspected drug-resistant TPE, every effort is warranted to isolate M. tuberculosis to perform drug susceptibility testing and provide guided therapy. For this purpose, the use of cultures or molecular methods with pleural biopsies is superior to their use in pleural fluid. If still M. tuberculosis cannot be detected, prolonged administration of ethambutol with isoniazid and rifampicin during the continuation phase of treatment might be considered.

Asbestos and the lung: highlights of a detrimental relationship.

Novel aspects of the pathogenesis of asbestos-related diseases are still coming to light http://ow.ly/EPDa30e8JqK.

Targeting Neovasculature with Multitargeted Antiangiogenesis Tyrosine Kinase Inhibitors in Non-small Cell Lung Cancer.

Chemotherapy has reached a plateau in the efforts for survival improvement in non-small cell lung cancer (NSCLC). The growing knowledge of NSCLC molecular pathobiology has led to the development of new treatments that target specific tumor functions. Angiogenesis is a tumor function leading to the formation of new tumor vessels that are crucial for its survival. Although vascular endothelial growth factor (VEGF) plays a primary role in angiogenesis, the inhibition of the VEGF pathway with VEGF-receptor (VEGFR) tyrosine kinase inhibitors (TKIs) is associated with a modest survival benefit due to the development of resistance by the tumor that has been mainly attributed to the up-regulation of other stimulators of angiogenesis. Thus, the use of multitargeted antiangiogenesis TKIs (MATKIs) for simultaneous inhibition of multiple angiogenic pathways has been proposed. This review summarizes data about novel treatment strategies incorporating the inhibition of angiogenesis with MATKIs in NSCLC. The data from all relevant studies shows that MATKIs do not offer additional survival benefit to currently available chemotherapeutic options in unselected NSCLC patients. However, the diversity in disease response to MATKI-containing regimens implies that specific patient subgroups may benefit from or be harmed by these agents. In this context, most studies agree that the VEGFR-targeting MATKIs are harmful in squamous NSCLC while specific MATKIs (i.e., motesanib, vandetanib and nintedanib) are associated with improved progression free survival in non-squamous NSCLC. However, overall survival benefit was found only in adenocarcinoma and Asian non-squamous NSCLC patients with the use of nintedanib and motesanib, respectively.

Pleural fluid tests to diagnose tuberculous pleuritis.

PURPOSE OF REVIEW: This article summarizes current data regarding the accuracy of pleural fluid tests assisting the diagnosis of tuberculous pleuritis (TBP). RECENT FINDINGS: No pleural fluid test reliably rules-in TBP in settings with low TBP prevalence. Interferon-γ) alone or in combination with adenosine deaminase (ADA) is more reliable than ADA for this purpose in nonlow prevalences. ADA can reliably rule-out TBP in prevalences of less than 40% although in higher prevalences the product of interleukin-27 and ADA is the most accurate rule-out test. SUMMARY: The definite diagnosis of TBP requires the isolation of Mycobacterium tuberculosis from pleural fluid or biopsies. Because of the low sensitivity of pleural fluid cultures and the invasiveness of pleural biopsy techniques, the concept of a pleural fluid test that accurately establishes or excludes TBP diagnosis has been proposed. Numerous pleural fluid tests have been evaluated for this purpose with ADA being the most widely accepted one. During the last years, it has been demonstrated that the ability of ADA to rule-in or rule-out TBP is affected by the prevalence of TBP in the setting where the test is used. The complementary use of interferon-γ or interleukin-27 increases the ability of ADA to rule-in or rule-out the disease, respectively.

Interleukin-27 improves the ability of adenosine deaminase to rule out tuberculous pleural effusion regardless of pleural tuberculosis prevalence.

BACKGROUND: Interleukin-27 (IL-27) has been proposed to be useful for diagnosing tuberculous pleural effusion (TPE). Adenosine deaminase (ADA) has been long used for the same purpose. The aim of this study was to compare the performance of IL-27, ADA, and their product (IL-27 • ADA) in the diagnosis of TPE. METHODS: Pleural fluid samples from patients with exudative pleural effusions were assessed for IL-27 and ADA levels. Receiver operating characteristic (ROC) curves were constructed to compare the overall diagnostic accuracy of IL-27, ADA, and IL-27 • ADA. Curves of false-positive (FPR) and false-negative (FNR) rates as a function of TPE prevalence were also constructed, and mean rates of false results in low (1-10%), intermediate (11-40%), and high (41-70%) prevalences were estimated to evaluate the ability of the three markers in ruling in or ruling out TPE. RESULTS: We studied 121 exudates. IL-27 and ADA were higher in TPEs compared with non-TPEs and they presented similar accuracies for the diagnosis of TPE. The product of IL-27 and ADA (IL-27 • ADA) was more accurate than ADA for the same purpose. IL-27 and IL-27 • ADA presented the lowest overall FPR and FNR, respectively. The FPR of IL-27, ADA and IL-27 • ADA was > 9%, even in high prevalence settings. Although their FNR was < 2% in low prevalence settings, only IL-27 • ADA exhibited sufficiently low FNR (< 1%) in intermediate and high prevalences. CONCLUSIONS: ADA, IL-27, and IL-27 • ADA cannot reliably 'rule in' TPE in any prevalence setting. TPE can be 'ruled out' by each of the biomarkers in low prevalence settings. In intermediate and high prevalence settings, IL-27 • ADA is a reliable 'rule out' test in the diagnostic approach to TPEs.

Diagnostic approach to the solitary pulmonary nodule.

The number of solitary pulmonary nodules (SPNs) detected each year is expected to increase dramatically with the implementation of lung cancer screening. Although some will have radiographic features highly specific for benignity, the rest are considered indeterminate and require further investigation. The management options include continued surveillance or immediate diagnostic sampling. The decision to proceed with immediate sampling is determined by nodule characteristics (i.e., density and size), and patient risk factors and preferences. Sampling is achieved either by surgical or by nonsurgical techniques, and the choice between the two is influenced by the probability of malignancy. Surgical methods are preferred in SPNs with high probability of malignancy because they provide both a definitive diagnosis and treatment in a single procedure. In contrast, when the probability of malignancy is low to moderate nonsurgical sampling is preferred. The following is a review of the diagnostic management options available when approaching an SPN.

Prognostic value of C-reactive protein in parapneumonic effusions.

BACKGROUND AND OBJECTIVE: Parapneumonic effusions (PPE) that require drainage are referred to as complicated parapneumonic effusions (CPPE). Following resolution of these effusions, residual pleural thickening (RPT) may persist. We hypothesize that the concentrations of CRP in pleural fluid (CRP(pf)) and serum (CRP(ser)) can be used to identify CPPE and to predict RPT. METHODS: All patients with non-purulent PPE, who were admitted to two tertiary hospitals during a 30-month period, were enrolled in the study. Baseline CRP(pf) and CRP(ser) levels were compared between patients with complicated or uncomplicated PPE, as well as between patients with or without RPT of >10 mm, 6 months after discharge from hospital. Cut-off values for identification of CPPE and prediction of RPT were determined by receiver operating characteristic curve analysis. Logistic regression analysis was performed to assess the association between CRP levels and RPT. RESULTS: Fifty-four patients were included in the study. Patients with CPPE (n = 23) had significantly higher levels of both CRP(pf) and CRP(ser) than those with uncomplicated PPE. For identification of CPPE, a CRP(pf) level >78.5 mg/L and a CRP(ser) level >83 mg/L gave 84% and 47% sensitivity, with 65% and 87% specificity, respectively. Classical criteria (pleural fluid pH <7.20, LDH >1000 IU/L, glucose <600 mg/L) were superior for this purpose. A combination of classical biomarkers with CRP levels using an 'AND' or 'OR' rule improved the positive and negative predictive values, respectively. CRP(ser) was an independent predictor for development of RPT (adjusted OR 1.18). A CRP(ser) level >150 mg/L had 91% specificity and 61% sensitivity for prediction of RPT. CONCLUSIONS: This study demonstrated the value of CRP(ser) for prediction of RPT in patients with PPE. Moreover, when used in combination with classical biomarkers, CRP levels may be a useful adjunct for decision-making in relation to treatment of patients with non-purulent PPE.

The efficacy of chest radiographs in detecting parapneumonic effusions.

BACKGROUND AND OBJECTIVE: Current guidelines recommend parapneumonic effusions (PPEs) with a thickness of ≥ 10 mm be sampled via thoracentesis. We hypothesized that anteroposterior (AP) CXRs are not as sensitive as posteroanterior (PA) and lateral radiographs in identifying PPEs and should not be routinely used in patients with suspected pneumonia. METHODS: Sixty-one hospitalized patients with pneumonia and PPE were retrospectively studied, all of whom had a CXR and CT scan within 24 h of each other. The CXRs of these patients were independently read by three pulmonologists for an effusion in each hemithorax, which was correlated with measured pleural fluid thickness on chest CT. RESULTS: Lateral, PA and AP radiographs were equivalent in identifying the presence of PPEs. All three views missed more than 10% of PPEs. The sensitivities of lateral, PA and AP CXRs were 85.7%, 82.1% and 78.4%, respectively (P = 0.749); the specificity was 87.5%, 81.3% and 76.4%, respectively (P = 0.198). The majority of effusions missed in each view were on films with lower lobe consolidation. CONCLUSIONS: All three CXR views missed effusions of a size significant enough to warrant thoracentesis. Consideration should be given to obtaining additional imaging at the time patients present with pneumonia, particularly in those with lower lobe consolidation.

Chylothorax: diagnostic approach.

PURPOSE OF REVIEW: This review evaluates recent research findings and proposes an up-to-date diagnostic approach for patients with suspected chylothorax. RECENT FINDINGS: Typically, chylothorax is a milky exudate with high triglyceride content (>110 mg/dl). However, milky appearance is not always the case and triglyceride levels can be less than 110 mg/dl, especially in fasting or malnourished patients. Transudative chylothoraces have been reported when cirrhosis, nephrosis or heart failure co-exist. In addition, although the vast majority of the white blood cells in chyle are lymphocytes, chylothoraces can be neutrophilic, especially the postsurgical ones. SUMMARY: Chylothorax is the accumulation of chyle into the pleural cavity usually due to thoracic duct leak and should be suspected not only in patients with milky effusions but also in the presence of certain co-morbidities or history of chest/neck trauma. Fluid triglycerides more than 110 mg/dl or less than 50 mg/dl virtually establish or exclude the diagnosis, respectively; ambiguous cases with values 50-110 mg/dl require lipoprotein analysis for the demonstration of chylomicrons. In fasting or malnourished patients lipoprotein analysis is suggested even with triglycerides less than 50 mg/dl. Typical pleural fluid in chylothorax is a lymphocytic exudate with low lactate dehydrogenase; atypical fluid characteristics (i.e. transudative nature, neutrophil-predominance or high lactate dehydrogenase) may be a sign of additional causes of pleural fluid accumulation.