Management of Malignant Pleural Effusion: Where Are We Now?

Pleural malignancies are among the most common causes of pleural disease and form the basis of our daily pleural practice. There has been significant research and increase in both diagnostic and therapeutic management of malignant pleural diseases in the last decade. Good-quality data have led to a paradigm shift in the management options of pleural malignancies, and indwelling pleural catheter is now recommended and widely used as first-line intervention. Several trials compared different treatment modalities for pleural malignancies and continue to emphasize the need to reduce hospital length of stay and unnecessary pleural intervention, and the importance of patient choice in clinical decision making. This practical review aims to summarize the current knowledge for the management of pleural malignancies, and the understanding of the steps that we still have to climb to optimize management and reduce morbidity.

Bifurcated Silicone Stents for the Management of Anastomotic Complications in Lung Transplanted Patients: Ten Years' Experience.

BACKGROUND: In lung transplantation (LT), the actual surgical practice is to cut the donor bronchus as short as possible in order to reduce anastomotic complications (AC). Consequently, the anastomosis is very close to the secondary carina. If AC occur, regular straight stents may be unsatisfactory and on-site modified bifurcated stents may represent an alternative. OBJECTIVES: This retrospective study sought to assess the short- and long-term outcomes of patients treated with customized bifurcated stent (CBS) for the management of AC following LT. METHODS: Data from patients with AC following LT requiring CBS placement between June 2010 and June 2020 were analyzed. RESULTS: Four hundred patients underwent lung transplant. AC requiring airway stenting occurred in 32 patients (8%), and CBS were inserted in 15 patients (3.5%). Indications were stenosis (n = 12; 80%) and bronchial dehiscence (n = 3; 20%). CBS were successfully deployed in 14 patients and failed in 1 patient. No migration was recorded during the follow-up. The median number of complication was 1 per patient (0-5). CBS could be removed in 11 patients (78.6%), and 3 died with their stents in place. AC recurrence or complications requiring new stenting occurred in 4/11 patients (36.3%), with a median time of 7 days (0-29). Seven patients (63.7%) had no AC recurrence, with a median follow-up of 925 days (118-3,249). CONCLUSIONS: The actual surgical anastomotic technique in LT provides new endoscopic challenges. CBS seem ideally positioned to address these difficulties safely and effectively but are associated with stent related complications requiring further endoscopic management.

A Rare Complication: Development of an Aspergilloma after Endobronchial Coil Placement in a COPD Patient.

Endobronchial coils are a relatively novel endoscopic lung volume reduction modality that aims to increase functional capacity in chronic obstructive pulmonary disease (COPD) patients. Two major trials have studied the safety and efficacy of this therapy, but long-term safety has not been studied. Adverse events reported are mainly periprocedural pneumothoraces and early bacterial infectious complications. We report the case of a patient with severe emphysema (Global Initiative for Chronic Obstructive Lung Disease stage IV COPD) who developed endobronchial coil-associated aspergillomas 3 years after coil placement.

Diagnostic Value of Computed Tomography Imaging Features in Malignant Pleural Mesothelioma.

BACKGROUND: Medical history, thoracentesis, and imaging features are usually the first steps in the investigation of a possible malignant pleural effusion (MPE). Unfortunately, the diagnostic yield of thoracentesis in this situation is suboptimal even if the procedure is repeated, especially in the context of malignant pleural mesothelioma (MPM). The next step for confirming the diagnosis, if clinically appropriate, is thoracoscopy, but not all patients are fit to undergo this procedure, so the diagnosis is then based on the medical history and imaging features only. OBJECTIVES: Our objective was to evaluate the diagnostic value of the medical history and imaging features in MPM. METHODS: We reviewed the imaging and medical charts of 92 patients with a final diagnosis of MPE included in our prospective medical thoracoscopy database. The clinical characteristics and imaging features of patients with primary MPE were compared with those of patients with secondary MPE. RESULTS: Male sex (82 vs. 59%, p = 0.02), asbestos exposure (58 vs. 10%, p < 0.001), and mediastinal (68 vs. 33%, p = 0.04), diaphragmatic (75 vs. 31%, p = 0.001) and circumferential pleural thickening (55 vs. 19% p = 0.001) were significantly more frequent in MPM patients. In a multivariate linear regression model, only asbestos exposure (OR 11.2; 95% CI 3.4-36.9) and circumferential pleural thickening (OR 4.7; 95% CI 1.6-13.9) were significantly associated with a diagnosis of MPM. CONCLUSION: In situations where it is impossible to obtain adequate pleural samples to differentiate MPM from a secondary pleural malignancy, the combination of circumferential pleural thickening and a history of asbestos exposure may be sufficient to make a clinical diagnosis.

An International Survey of Mediastinal Staging Practices amongst Interventional Bronchoscopists.

INTRODUCTION: In potentially curable non-small-cell lung cancer, different practice guidelines recommend invasive me-diastinal staging in tumors larger than 3 cm, central, or hy-permetabolic N1 lymph nodes. There is no consensus concerning the use of an endosonographic procedure or a mediastinoscopy in the first line in patients with a radiologically normal mediastinum, while in case of a mediastinal involvement, the latest European guidelines recommend the combination of endobronchial ultrasound (EBUS) and endoscopic ultrasound/endoscopic ultrasound with EBUS endoscope (EUS/EUS-B), using a systematic endosonographic procedure. This international survey was conducted to describe current medical practices in endoscopic mediastinal staging amongst interventional bronchoscopists. METHODS: A survey was developed and sent to all members of different interventional pulmonology societies, with the purpose to describe who, when and how an endoscopic mediastinal staging was performed. RESULTS: One hundred and fifty-three bronchoscopists responded to the survey. Most of them practiced in Europe (n = 84, 55%) and North America (n = 52, 34%). In the first line, EBUS alone was the most widely used endoscopic procedure for mediastinal staging. Half of the responders performed a systematic endoscopic staging procedure, including a systematic examination of all accessible nodal stations and a sampling of all lymph nodes >5 mm in the short axis at each station. A higher proportion of bronchoscopists who have completed a dedicated fellowship program performed systematic endoscopic mediastinal staging. Few endoscopists routinely perform combined EBUS/EUS(-B) for mediastinal staging and use the combination only in selected cases. CONCLUSION: There are several areas of divergence between published guidelines and current practices reported by interventional bronchoscopists. EBUS alone is the most widely used endoscopic procedure for mediastinal staging in lung cancer, and a combined endoscopic approach is frequently omitted by the responders. A fellowship program appears to be associated with a higher rate of systematic endoscopic staging procedures.

miR-9 Does Not Regulate Lamin A Expression in Metastatic Cells from Lung Adenocarcinoma.

In lung adenocarcinoma, low lamin A expression in pleural metastatic cells has been proposed as a pejorative factor. miR-9 physiologically inhibits the expression of lamin A in neural cells and seems to be a central actor in the carcinogenesis and the metastatic process in lung cancer. Thus, it could be a good candidate to explain the reduction of lamin A expression in lung adenocarcinoma cells. miR-9 expression was analyzed in 16 pleural effusions containing metastatic cells from lung adenocarcinoma and was significantly reduced in patients from the 'Low lamin A expression' group compared to patients from the 'High lamin A expression' group. Then, carcinoma cells selection by fluorescence-activated cell sorting (FACS) was performed according to epithelial membrane antigen (EMA) expression, reflecting lamin A expression. miR-9 was underexpressed in lamin A- carcinoma cells compared to lamin A+ carcinoma cells in patients from the 'Low lamin A expression' group, whereas there was no difference of miR-9 expression between lamin A+ and lamin A- carcinoma cells in patients from the 'High lamin A expression' group. These results suggest that miR-9 does not regulate lamin A expression in metastatic cells from lung adenocarcinoma. On the contrary, miR-9 expression was shown to be reduced in lamin A-negative carcinoma cells.

Detection of EGFR, KRAS and BRAF mutations in metastatic cells from cerebrospinal fluid.

BACKGROUND: In lung adenocarcinoma, molecular profiling of actionable genes has become essential to set up targeted therapies. However, the feasibility and the relevance of molecular profiling from the cerebrospinal fluid (CSF) in the context of meningeal metastasis have been poorly assessed. METHODS: We selected patients with stage IV lung adenocarcinoma harbouring metastatic cells in the CSF after cytological analysis. Seven samples from six patients were eligible for molecular testing of epidermal growth factor receptor (EGFR), V-Ki-ras2 Kirsten rat sarcoma viral oncogene homologue (KRAS), v-Raf murine sarcoma viral oncogene homologue B1 (BRAF) and human epidermal growth factor receptor 2 (HER2) mutations using quantitative polymerase chain reaction (PCR) high-resolution melting curve analysis and Sanger sequencing after DNA extraction from the cell pellets of the CSF. RESULTS: Five patients showed mutations in one or two actionable genes, two harboured an EGFR mutation (exons 19 and 21), one only a KRAS mutation, one both EGFR and KRAS mutations and one a BRAF mutation. In all cases, the results of mutation testing provided new major information for patient management, leading to therapeutic adaptation. CSF molecular analysis identified mutations not detected in other neoplastic sites for two patients. In one case, the EGFR p.Thr790Met was identified. CSF was also the only sample available for genetic testing for almost all patients at the time of disease progression. CONCLUSIONS: When cancer cells are present in the CSF, the molecular profiling from the cell pellets is relevant, as it can detect supplemental or different mutations compared to a previous analysis of the primitive tumour or plasma cell-free DNA and allows the adaptation of the treatment strategy.

Experience with Transcordal Silicone Stents in Adult Laryngotracheal Stenosis: A Bicentric Retrospective Study.

BACKGROUND: Benign stenosis involving laryngeal and upper tracheal structures represents a therapeutic challenge. Open surgery and endoscopic management have to be discussed by a multidisciplinary board in order to evaluate the risk and benefit for each patient. OBJECTIVE: The objective of this retrospective study was to report the experience of two French centers with transcordal silicone stents (TSS) in the endoscopic management of benign laryngotracheal stenosis (BLTS) in adults, with focus on efficacy, safety, and tolerability. METHODS: We performed a retrospective chart review of all cases of BLTS treated with TSS between January 2001 and June 2017 at two tertiary centers in France: the Centre Hospitalier Régional Universitaire de Strasbourg and the Hôpital Nord de Marseille. RESULTS: A total of 17 patients were included. Eleven had a tracheostomy at initial management which consisted of 8 T-tubes and 9 strictly endoluminal stents placements. The main complications were minor aspirations in 5 patients (29%), granulation in 3 patients (18%), migration in 2 patients (12%), and severe dysphonia in 3 patients (18%). After a mean duration of 18.3 months, 11 patients (65%) had had their TSS definitely removed, 13 patients were tracheostomy free (76%), and a TSS remained in place in 4 patients (24%). CONCLUSIONS: Adult BLTS treatment with TSS placement is associated with low morbidity and excellent clinical outcomes, with a large proportion of patients free of airway instrumentation on long-term follow-up.

Diagnostic Accuracy of Lateral Decubitus Chest Radiography before Pleural Maneuvers for the Management of Pleurisies in the Era of Chest Ultrasound.

BACKGROUND: Chest ultrasound (CUS) is the gold standard to detect pleural adhesions before pleural maneuvers. However, the CUS technique is not available in all countries where the assessment is only based on clinical examination and chest radiography. OBJECTIVE: To assess the value of lateral decubitus chest radiography (LDCR) to detect pleural adhesions. METHODS: Consecutive patients with pleural effusions undergoing LCDR followed by medical thoracoscopy the day after were identified from an institutional database. The diagnostic sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy for LDCR were calculated. RESULTS: Eighty-six patients were included in the study. The sensitivity, specificity, PPV, and NPV of LDCR for the presence of adhesions taking into account the shape of the horizontal level were 71.2% (56.7-82.5), 44.1% (27.6-61.9), 66.1% (52.1-77.8), and 50% (31.7-68.3), respectively. The accuracy to predict pleural adhesions for the sign "incomplete horizontal level" was 60.5 (49.3-70.7). The accuracy to predict pleural adhesions in case of irregular aspect of the horizontal level was 53.5 (42.5-64.2). CONCLUSIONS: The accuracy of LDCR for the detection of pleural adhesions is low in patients with pleural effusion and LDCR is not sufficient before pleural maneuvers. This has to be taken into account in countries with a high prevalence of pleural tuberculosis which usually lead to loculated pleural effusions. CUS has to be urgently included in dedicated educational programs in these areas in order to decrease the complications related to unexpected pleural adhesions and achieve better planning for the management of pleural effusions.

Safety and Efficacy of a Fully Covered Self-Expandable Metallic Stent in Benign Airway Stenosis.

BACKGROUND: The use of self-expandable metallic stents (SEMS) in benign airway disease was the object of a boxed warning from the United States Food and Drug Administration in 2005 due to the risk of stent-related complications and difficulties associated with their removal. Third-generation fully covered SEMS have been commercialized since this warning and theoretically should not present the same difficulties associated with removal as they cannot become embedded in the airway mucosa. OBJECTIVES: We aimed to examine the safety and efficacy of a specific third-generation SEMS, the Silmet stent. METHODS: We reviewed the records of all patients treated for benign airway stenosis with third-generation Silmet SEMS from January 2011 to December 2015 at the North Hospital of Marseilles, France. RESULTS: Forty SEMS were inserted in 30 patients over this period. Twenty (50.0%) stents were removed because of stent-related complications after a median of 77.0 ± 96.6 days (migration 32.5%, granulation tissue formation 7.5%, subjective intolerance 5.0%, mucus plugging 2.5%, laryngeal edema 2.5%). There were no cases of stent-related mortality. All complications were managed successfully endoscopically. Thirty-six stents (90.0%) were removed successfully after a median of 122.0 ± 113.2 days without any complications. The clinical success rate of stent treatment was 40.7%. CONCLUSION: Third-generation SEMS are a safe treatment option for complex benign airway stenosis, but complications requiring stent removal are frequent. Further studies are needed to compare the performance of third-generation SEMS and silicone stents in benign airway stenosis.

Does the LENT score risk-stratify patients with malignant pleural mesothelioma? An observational study.

BACKGROUND: Malignant pleural mesothelioma (MPM) is a rare, highly aggressive and deadly disease with a poor patient life expectancy. A few years ago, the main challenge was the histological diagnosis of this disease; at present, the search for the best therapeutic strategy is now a priority. However, an optimal therapeutic strategy is not yet clear, despite growing efforts in the treatment armamentarium and research, and at the era of tailored and individualized treatment, tools to predict patient survival are needed for therapeutic decision-making. Among them, the LENT scoring system was developed to predict prognosis in patients with malignant pleural effusion. The aim of this study was to assess the performance of the LENT score in predicting prognosis in patients with MPM. METHODS: A retrospective observational study was conducted by analyzing the prospective collected databases of patients undergoing medical thoracoscopy in a single center with a final diagnosis of MPM confirmed by the MESOPATH National Reference Center. RESULTS: A total of 41 patients with MPM were studied. All patients underwent platinum-based chemotherapy combined with pemetrexed ± bevacizumab. No high-risk category patients were found using the LENT scoring system in this cohort. The median (range) LENT score at the time of medical thoracoscopy was 0 (0-3) and the median survival was 15.5 (2-54) months for the entire cohort. The median survival of low-risk and moderate-risk category patients was 21.4 months (2-54, 32 patients) and 6.7 months (2-19, nine patients), respectively. A total of 27 patients with MPM of epithelial subgroup had a median LENT score of 1 (0-2) with a 26 (2-54) months median survival. The median LENT score and median survival of nonepithelial mesothelioma patients (biphasic MPM subgroup, eight patients; sarcomatoid MPM subgroup, six patients) were 0 (0-3) and 11 (2-52) months, respectively. CONCLUSIONS: Applied to a homogenous cohort of MPM patients, the LENT score underestimated prognosis and was not useful per se for the management of this disease, as evidenced in the epithelial mesothelioma subgroup of patients in our study.

Advances in pleural infection and malignancy.

Pleural infection and malignancy are among the most common causes of pleural disease and form the mainstay of pleural practice. There has been significant research and increase in scientific understanding in these areas in the past decade. With regard to pleural infection, the rising incidence remains worrying. An increased awareness allowing earlier diagnosis, earlier escalation of therapy and the use of validated risk stratification measures may improve outcomes. In pleural malignancy, research has enabled clinicians to streamline patient pathways with focus on reducing time to diagnosis, definitive management of malignant pleural effusion and achieving these with the minimum number of pleural interventions. Trials comparing treatment modalities of malignant pleural effusion continue to highlight the importance of patient choice in clinical decision-making. This article aims to summarise some of the most recent literature informing current practice in these two areas.

Saline lavage for the management of severe pleural empyema: A cohort study.

BACKGROUND: Despite advances in the treatment of pleural infection, up to 20% of patients die. So far, studies assessing the role of intrapleural saline lavage for the management of all stage pleural infections are very scarce, usually excluding patients with cancer. METHODS: The method used was a retrospective cohort study including pleural empyema managed with a pleural lavage of saline solution through a small-bore chest tube. The primary outcome was the rate of failure at 3 months (surgical referral or additional pleural manoeuver due to recurrent infection or all-cause mortality). Secondary outcomes were hospital stay, the change of the chest radiograph and inflammatory biomarkers, and complications. RESULTS: Thirty patients with pleural empyema were included, 11 (36.7%) with an active cancer. The overall rate of failure at 3 months was 13.3% (surgical referral = 0; additional pleural manoeuver = 3; mortality = 1). Median length of pleural lavage and hospital stay were, respectively, 14 days (7-28) and 17 days (11-42). Inflammatory markers and size of the effusion on chest radiograph significantly decreased for Day 0 to Day 14. No chest tube blockade was reported, but seven (23.3%) accidentally withdrew. No other side effects were reported. CONCLUSIONS: Intrapleural saline lavage is efficient and safe for the management of pleural empyema, even in severe status patients with cancer, at the cost of a prolonged hospitalization.

A Prediction Model to Optimize Invasive Mediastinal Staging Procedures for Non-small Cell Lung Cancer in Patients With a Radiologically Normal Mediastinum: The Quebec Prediction Model.

BACKGROUND: Current guideline-recommended criteria for invasive mediastinal staging in patients with a radiologically normal mediastinum fail to identify a significant proportion of patients with occult mediastinal disease (OMD), despite it leading to a large number of invasive staging procedures. RESEARCH QUESTION: Which variables available before surgery predict the probability of OMD in patients with a radiologically normal mediastinum? STUDY DESIGN AND METHODS: We identified all cTxN0/N1M0 non-small cell lung cancer tumors staged by CT imaging and PET with CT imaging in our institution between 2014 and 2018 who underwent gold standard surgical lymph node dissection or were demonstrated to have OMD before surgery by invasive mediastinal staging techniques and divided them into a derivation and an independent validation cohort to create the Quebec Prediction Model (QPM), which allows calculation of the probability of OMD. RESULTS: Eight hundred three patients were identified (development set, n = 502; validation set, n = 301) with a prevalence of OMD of 9.1%. The developed prediction model included largest mediastinal lymph node size (P < .001), tumor centrality (P = .23), presence of cN1 disease (P = .29), and lesion standardized uptake value (P = .09). Using a calculated probability of more than 10% as a threshold to identify OMD, this model had a sensitivity, specificity, positive predictive value, and negative predictive value in the derivation cohort of 73.9% (95% CI, 58.9%-85.7%), 81.1% (95% CI, 77.2%-84.6%), 28.3% (95% CI, 23.4%-33.8%), and 96.8% (95% CI, 95.0%-98.1%), respectively. It performed similarly in the validation cohort (P = .77, Hosmer-Lemeshow test; P = .5163, Pearson χ2 and unweighted sum-of-squares statistics; and P = .0750, Stukel score test) and outperformed current guideline-recommended criteria in identifying patients with OMD (area under the receiver operating characteristic curve [AUC] for American College of Chest Physicians guidelines criteria, 0.65 [95% CI, 0.59-0.71]; AUC for European Society of Thoracic Surgeons guidelines criteria, 0.60 [95% CI, 0.54-0.67]; and AUC for the QPM, 0.85 [95% CI, 0.80-0.90]). INTERPRETATION: The QPM allows the clinician to integrate available information from CT and PET imaging to minimize invasive staging procedures that will not modify management, while also minimizing the risk of unforeseen mediastinal disease found at surgery.

Pulmonary cement embolism complicating percutaneous kyphoplasty: A case report.

BACKGROUND: Vertebral cement augmentation procedures, as kyphoplasty (KP) or percutaneous vertebroplasty (PVP), are commonly used for the management of pain of the vertebral column usually due to fractures related to traumatic injury, osteoporosis or metastatic lesion. It is a useful and safe technique with few complications. Among them, symptomatic pulmonary cement embolism (PCE) can happened, even rarely described in the literature, leading to severe cardio-respiratory manifestations depending on the location and size of the cement emboli. CASE PRESENTATION: A 55 yo woman presented with atypical chest pain and presyncope three weeks after a motor vehicle accident resulting in an L1 compression fracture treated with kyphoplasty. She was hemodynamically stable. Blood tests showed D-Dimer 0.29 µg/mL, troponin <5ng/mL, Brain Natriuretic Protein 14 ng/mL and a PaO2 of 99 mmHg on arterial blood gas analysis. A computed tomography scan of chest showed linear hyperdense foreign bodies in two segmental pulmonary arteries at the level of middle lobe and right lower lobe compatible with pulmonary cement embolism. Anticoagulation with rivaroxaban for sixth months resulted in resolution of symptoms. CONCLUSIONS: In this case, the pulmonary cement embolism occurred after kyphoplasty, which is associated with less risk of PCE than vertebroplasty. The procedure was done under biplanar fluoroscopy and no leakage of cement was noted, which would raise suspicion for CPE. Repeat imagine after this procedure is not routinely done. This case demonstrates that systematic imaging post procedure should be considered.An anticoagulation with rivaroxaban seems to be effective in our patient.

Central location and risk of imaging occult mediastinal lymph node involvement in cN0T2-4 non-small cell lung cancer.

BACKGROUND: Appropriate pre-operative staging is a cornerstone in the treatment of non-small cell lung cancer (NSCLC). Central location and size greater than 3 cm are amongst indications for pre-operative invasive mediastinal staging but the quality of the evidence behind this recommendation is low. METHODS: We retrospectively reviewed all cases of cT2-4N0M0 NSCLCL after CT and TEP-CT which underwent surgical resection with lymph node dissection or had a positive invasive pre-operative mediastinal staging in our institution from 2014 to 2018. RESULTS: Three hundred and ten patients met inclusion criteria, 79 (25.5%) central and 231 (74.5%) peripheral tumors. Central tumor location was associated with a higher prevalence of pN2-3 disease (17.7% vs. 6.1%, P<0.001). In a multivariate analysis, central tumor location remained the only factor statistically associated with imaging occult mediastinal disease (OR 3.23, 95% CI: 1.45-7.18). NPV of PET-CT for occult mediastinal disease was 0.83 (95% CI: 0.72-0.90) in central and 0.94 (95% CI: 0.90-0.97) in peripheral tumor. Central location was also associated with a higher prevalence of occult N1 to N3 disease (43.0% vs. 15.2%, P<0.001). CONCLUSIONS: This study suggests that invasive mediastinal staging is required in central cT2-4N0 NSCLC but can be questioned in peripheral one, especially in cT2N2 subgroup if the patient is a candidate for lobar resection.

Prolonged survival after multimodal therapy for pleural mesothelioma: Don't give up the follow-up. A case report.

Malignant Pleural mesothelioma (MPM) is a rare disease which is associated with a poor prognosis. Front line chemotherapy represents the cornerstone in the management of MPM, and the place of radical surgery is controversial and reserve in early-stage disease. However prolonged survival (more than 24 months) can be observed in rare cases and only in the context of multimodal treatment including surgical management. We report the case of a patient suffering from an epithelial MPM with a 14-years progression-free survival after trimodal treatment including extrapleural pneumonectomy followed by chemotherapy and radiotherapy. This case illustrates that despite being an aggressive disease, multimodal management including radical surgery may allow a prolonged response in MPM but requires a whole-life surveillance.

Cerebral Air Embolism After Pleural Lavage for Empyema.

Percutaneous pleural maneuvers are performed routinely in the management of pleural diseases with a favorable safety profile. We report a case of cerebral air embolism during a pleural lavage for the management of an empyema. This severe complication is rarely reported in the literature, although it can happen after any percutaneous thoracic procedures. Asymptomatic arterial air emboli can occur in up to 5% of percutaneous thoracic maneuvers. Diagnosis should be made upon sudden neurologic signs and confirmed with brain imaging. Standard treatment is based on hyperbaric oxygen therapy, and it can be performed safely with an intrapleural catheter.