Review of the Physiology and Anesthetic Considerations for Pleuroscopy/Medical Thoracoscopy.

Pleuroscopy or medical thoracoscopy is the second most common utilized procedure after bronchoscopy in the promising field of interventional pulmonology. Its main application is for the diagnosis and management of benign or malignant pleural effusions. Entry into the hemithorax is associated with pain and patient discomfort, whereas concurrently, notable pathophysiologic alterations occur. Therefore, frequently procedural sedation and analgesia is needed, not only to alleviate the patient's emotional stress and discomfort by mitigating the anxiety and minimizing the pain but also for yielding better procedural conditions for the operator. The scope of this review is to present the physiologic derangements occurring in pleuroscopy and compare the various anesthetic techniques and sedative agents that are currently being used in this context.

Two years progression-free survival under vinorelbine metronomic therapy of a patient with metastatic epithelioid hemangioendothelioma.

Epithelioid hemangioendothelioma (EHE) is a very rare vascular tumor, originating from endothelial cells. The etiology of EHE is unknown, yet at the molecular level, different angiogenic stimulators may act as promoters of endothelial cell proliferation. The tumor affects more commonly the lung, the liver and the bones but it can affect any other organ. Due to its heterogeneous presentation and its rarity it is often misdiagnosed. No treatment is proved to be efficient in metastatic EHE and the median survival of patients with metastatic pleural disease is generally poor, less than one year. we report a case of a 57-year-old female with multiple metastatic EHE including pleural, diagnosed by medical thoracoscopy, with a progression-free survival of 24 months with oral vinorelbine as maintenance therapy after combination of cisplatin-vinorelbine. We believe that this therapy might be of value to test in this patient population as it has never been tested before.

Chest ultrasound findings in usual interstitial pneumonia patterns: a pilot study.

It is unknown what role chest ultrasound plays in distinguishing the various usual interstitial pneumonia (UIP) patterns of high-resolution chest tomography (HRCT). The purpose of this study was to see if there was a link between the results of chest ultrasound (u/s) and HRCT in patients with idiopathic pulmonary fibrosis (IPF). We performed chest u/s in 16 patients with UIP and probable UIP patterns to indeterminate UIP and alternative diagnosis patterns in this single center prospective study to determine any possible relationship with the HRCT findings. A chest radiologist reviewed each HRCT to determine the pattern in accordance with the American Thoracic Society (ATS) / European Respiratory Society (ERS) Guidelines. The local multidisciplinary committee validated the patients' diagnoses before they were included. When compared to the indeterminate for UIP or alternative diagnosis pattern group, there was a trend (p=0.07) toward the presence of more B lines in UIP or probable UIP patterns. There was no statistically significant difference in the presence of small, large, white lung, or pleural line thickening >5mm. Subgroup analysis revealed that patients with honeycombing were more likely to have a fragmented pleural line (p=0.04). To summarize, in our pilot study, chest u/s appears unable to differentiate UIP and probable UIP patterns from indeterminate UIP and alternative diagnosis patterns. However, it appears that this technique can be used to recognize the honeycombing pattern.

Medical Thoracoscopy Implementation after a European Respiratory Society Course Held from 2003 to 2016: A Survey.

BACKGROUND: Medical thoracoscopy (MT) is an important procedure in the management of patients with pleural diseases. OBJECTIVES: We designed a survey to explore whether the participants of our courses implement MT at their hospital after attending the course as no real-life data exist. METHODS: We distributed by e-mail a questionnaire to the participants of the courses. The questionnaire included general information about the participants, the precourse experience on MT, the postcourse implementation of the technique, and the reasons for failure. RESULTS: Responses were obtained from 104 of 324 (32.3%) identified emails. Responders were males (76%), seniors (59.7%), respiratory physicians (91.3%), working in a public/university hospital (78.8%), and mostly beginners (65.3%) from 41 countries. Following the course, 58.6% of responders either created or modified a MT program in their workplace. The reasons for not performing MT before the course were as follows: patients' referral to a thoracic surgeon, not enough training, lack of funding, department understaffed, and refusal by the hospital/department. Overall, these reasons were significantly decreased (p = 0.002) after the course. CONCLUSIONS: Real-life data of our survey suggest that more than half of the responders have implemented the technique or modified their practice according to the skills they got from the course.

Local Anesthesia Thoracoscopy with versus without Midazolam: A Randomized Controlled Trial.

BACKGROUND: Medical thoracoscopy is the gold standard for the diagnosis of pleural diseases. To date, no consensus exists regarding the choice of sedative and analgesic agents in patients undergoing local anesthetic thoracoscopy (LAT), and questions are raised as to whether sedatives may add to respiratory side effects. OBJECTIVE: The aim of the study was to test the hypothesis that administration of midazolam associated with lidocaine versus lidocaine alone in patients with LAT adds to respiratory side effects. METHODS: We randomly assigned 80 patients to a 1:1 study to 2 groups: local anesthesia by lidocaine (n = 40) versus lidocaine and midazolam (n = 40), with the primary end point being the mean lowest oxygen saturation. The secondary end points were cardiovascular parameters, complications, days of drainage, hospital stay, and patients' quality of life (QoL) as assessed by a visual analog scale (VAS). RESULTS: The mean age of all patients was 66.6 ± 13.1 years. The study comprised 50 males (62.5%). No difference was observed in the demographics between the 2 groups. No significant difference was observed between the 2 groups in oxygen saturation (primary end point). A significant difference was observed in favor of the midazolam group regarding the QoL assessed by VAS. CONCLUSION: Midazolam does not add to respiratory side effects when it is used with lidocaine for LAT, while patients' QoL is actually improved in this group. Therefore, in our department, we changed our startegy in favor of the association of lidocaine and midazolam.

Reduced Serum Vitamin D Levels Are Associated with Insulin Resistance in Patients with Obstructive Sleep Apnea Syndrome.

Background and objectives: Obstructive sleep apnea syndrome (OSAS) is associated with cardiovascular and metabolic risk factors, such as insulin resistance. Furthermore, OSAS has been associated with decreased levels of vitamin D (Vit D). The aim of the study was to assess the association between Vit D levels (expressed as 25(OH)D serum levels) and insulin resistance in patients with OSAS. Materials and Methods: Serum 25(OH)D levels were measured in consecutive subjects who had undergone polysomnography and pulmonary function testing. OSAS patients were divided into those with (homeostatic model assessment [HOMA-IR] ≥ 2) and without insulin resistance (HOMA-IR < 2). Results: Overall, 92 patients (81 males) were included in the study. OSAS patients with insulin resistance significantly differed from those without insulin resistance in terms of the body-mass index (BMI) (36.3 ± 5.8 compared to 32 ± 5.6 kg/m2, respectively, p = 0.001), apnoea-hypopnoea index (AHI) (57.4 ± 28.9 compared to 40.9 ± 27.9 events/h, respectively, p = 0.009) and indices of hypoxia during sleep. Patients with OSAS and insulin resistance had lower levels of serum 25 (OH) D compared with OSAS but without insulin resistance (19.3 ± 11.5 vs 26.7 ± 12.2 ng/mL, respectively, p = 0.005). Regression analysis demonstrated a negative association of 25(OH)D levels (ß = -0.048, odds ratio [OR]: 0.953, 95% confidence interval [CI]: 0.913-0.995, p = 0.030) and a positive association of BMI (ß = 0.110, OR: 1.116, 95% CI: 1.007-1.237, p = 0.036) with insulin resistance. Conclusions: Vit D insufficiency was significantly more frequent among OSAS patients with insulin resistance. Both low 25(OH)D levels and high BMI were associated with the risk of insulin resistance in this population.

Efficacy of Whole-Lung Lavage in Pulmonary Alveolar Proteinosis: A Multicenter International Study of GELF.

BACKGROUND: New therapies have emerged in the treatment of pulmonary alveolar proteinosis (PAP) and, therefore, there is a real need to evaluate the efficacy of whole-lung lavage (WLL) in this rare disease. OBJECTIVES: The aim of this study was to assess the efficacy of WLL in patients with PAP. METHODS: We included 33 patients from 12 centers, which are members of the French-Speaking Thoracic Endoscopy Group, for analysis. Data collection concerned patients and disease characteristics, pulmonary function tests (PFTs) and technical information on the procedure. RESULTS: The median age of the patients was 44 years (range 13-77). There were 23 (71.9%) patients with respiratory insufficiency at presentation. All patients underwent WLL by general anesthesia and selective lung ventilation, except 1 who underwent awake flexible bronchoscopy. We noted differences in the technique, as 12 (36.36%) patients had percussion during the procedure and only 4 (12.1%) patients underwent 2-lung lavage during 1 anesthesia. A median of 12 L was used to perform WLL (1.0-40 L). Complications occurred in 11 (33.3%) patients, and 18 (56.25%) of them relapsed in a median period of 16.9 months. No significant changes were found in any PFT parameters studied, except for PaO2, which was significantly improved by 6.375 mm Hg (p = 0.0213) after the procedure compared to before. CONCLUSIONS: Although the application of the WLL technique was variable, overall, it significantly improved patients' short-term respiratory condition by improving PaO2. However, a long-term effect needs to be confirmed, as many of our patients relapsed.

Bilateral empyema treated by sequential pleuroscopy.

Bilateral empyema associated to infectious pericarditis is an extremely rare, yet life-threatening condition. Pleuroscopy-medical thoracoscopy has proved its efficacy in series of patients with empyema. Yet, all reported cases treated by this technique, concerned patients with pleural infection located to a single hemithorax. We present the case of a 71-year-old man with bilateral empyema treated successfully by sequential pleuroscopy, associated to infectious pericarditis.

Prognostic factors in patients presenting with pleural effusion revealing malignancy.

BACKGROUND: The survival of patients with malignant pleural effusion is considered generally poor. Most of the studies reporting results of prognostic factors are retrospective, using pleural thoracentesis for diagnosis. The objectives of our study were to reveal possible prognostic factors in patients initially presenting with undiagnosed pleural effusion proven to be malignant by diagnostic thoracoscopy. METHODS: Ninety consecutive patients, 48 of whom were male (53%), with a median age of 69 years (range 37-93) and a performance status (PS) of 0/1 (63%) and with initially undiagnosed pleural effusion that was proven to be malignant by thoracoscopy were evaluated. Survival time was defined as the time from thoracoscopic diagnosis to death or the last follow-up. A regression analysis was used to determine significant clinical and biological prognostic factors. RESULTS: Lung carcinoma (44.4%), breast carcinoma (24.4%), and mesothelioma (12.2%) were the most frequent tumors diagnosed. The median overall survival was 11 months (range 0.5-55). The survival of the patients was related to the following factors: histology of the primary tumor (p = 0.008), PS (p < 0.001), white blood cells (p = 0.018), and the blood neutrophil-to-lymphocyte (N/L) ratio (p = 0.002). Multiple regression showed PS, histology, and the N/L ratio. CONCLUSION: The factors affecting survival in our patients were PS, primary tumor histology, and the N/L ratio. These factors may help physicians select patients for treatment and/or interventional procedures.

Effect of compliance to continuous positive airway pressure on exacerbations, lung function and symptoms in patients with chronic obstructive pulmonary disease and obstructive sleep apnea (overlap syndrome).

INTRODUCTION: Patients with overlap syndrome (OS), that is obstructive sleep apnea (OSA) and chronic obstructive pulmonary disease (COPD), are at increased risk of acute exacerbations related to COPD (AECOPD). We assessed the effect of CPAP compliance on AECOPD, symptoms and pulmonary function in OS patients. METHODS: Consecutive OS patients underwent assessment at baseline and at 12 months under treatment with CPAP of: AECOPD and hospitalizations, COPD Assessment Test (CAT) and modified British Medical Research Council (mMRC) questionnaires, pulmonary function testing and 6-min walking test (6MWT). RESULTS: In total, 59 patients (54 males) with OS were followed for 12 months and divided post hoc according to CPAP compliance into: group A with good (≥4 h CPAP use/night, n = 29) and group B with poor (<4 h CPAP use/night, n = 30) CPAP compliance. At 12 months, group A showed improvements in FEV1 (p = 0.024), total lung capacity (p = 0.024), RV/TLC (p = 0.003), 6MWT (p < 0.001) and CAT (p < 0.001). COPD exacerbations decreased in patients with good CPAP compliance from baseline to 12 months (17 before vs. 5 after, p = 0.001), but not in those with poor compliance (15 before vs. 15 after, p = 1). At multivariate regression analysis, COPD exacerbations were associated with poor CPAP compliance (ß = 0.362, 95% CI: 0.075-0.649, p = 0.015). CONCLUSIONS: When compared to poorly compliant patients, OS patients with good CPAP compliance had a lower number of AECOPD and showed improved lung function and COPD related symptoms.

Clinical Outcomes Beyond 1L EGFR-TKI Progression in mNSCLC: Final Results of the Real-World Study 'LUNGFUL'.

BACKGROUND/AIM: Real-world data on the EGFR mutational profile upon progression after first/second-generation EGFR-TKI treatment in patients with advanced non-small-cell lung cancer (NSCLC) and treatment strategies employed thereon are needed. PATIENTS AND METHODS: This observational study was conducted in 23 hospital-based lung cancer Centers in Greece (protocol code: D133FR00126). Ninety-six eligible patients were consecutively enrolled between July-2017 and September-2019. Re-biopsy was performed in 18 of 79 patients who tested T790M-negative in liquid biopsy after progression in the first-line (1L) setting. RESULTS: Of the study population, 21.9% tested T790M-positive, while 72.9% proceeded to 2L treatment, mainly comprising of a third-generation EGFR-TKI (48.6%), a switch to chemotherapy (30.0%), or chemo-immunotherapy (17.1%). The objective response rate (ORR) in 2L was 27.9% in T790M-negative and 50.0% in T790M-positive patients. Of evaluable patients, 67.2% experienced disease progression; median progression-free survival (PFS) was 5.7 and 10.0 months among T790M-negative and positive patients, respectively. Among T790M-negative patients, longer median PFS and post-progression survival were observed with third-generation EGFR-TKI treatment. CONCLUSION: Mutational status and treatment strategy were identified as critical determinants of clinical outcomes in the 2L-setting of EGFR-mutated NSCLC patients in real-world settings in Greece, with early diagnosis, appropriate molecular testing and high-efficacy treatments at first lines positively affecting ORR and PFS.

Pleural effusion in lung cancer: more questions than answers.

Lung cancer remains the most common fatal malignancy, despite more aggressive therapies. Few patients will survive 5 years, as up to 80% of the patients will present with advanced-stage disease at diagnosis. Chemotherapy offers little benefit in terms of median survival and disease-free survival in patients with advanced-stage non-small-cell lung carcinoma (NSCLC). In the last decade, the development of new targeted therapies based on the better understanding of different paths of carcinogenesis has given new hope to both physicians and patients. Metastatic pleural effusion from lung cancer has a particularly poor prognosis, and in NSCLC it is actually reclassified as stage IV disease. A possible explanation of this observation is differences in the genomics between primary tumors and metastasis, leading to possible different therapeutic approaches with novel molecular therapies in this patient population. The current review aims to summarize the actual situation of research in pleural disease due to lung carcinoma in relation to novel targeted therapies tested in this patient population.

Subpleural versus deep lung biopsies obtained during pleuroscopy for histological examination: an experimental animal study.

BACKGROUND: Lung biopsies obtained during medical pleuroscopy using coagulating forceps could represent a cost-effective alternative to surgical lung biopsies in patients with diffuse parenchymal lung diseases (DPLD). However, it is not clear whether these patients should undergo deeplung biopsies rather than more superficial subpleural lung biopsies. OBJECTIVES: The aim of this experimental animal study was to compare gross and microscopic features of deep and subpleural pleuroscopic lung biopsy samples. METHODS: Six male sheep (median weight 40 kg) underwent lung biopsies via pleuroscopy under general anesthesia. The following parameters were studied: weight, size, quality of the parenchyma and visceral pleura, parenchymal vessels and bronchial tissue. RESULTS: The mean number of biopsies taken per animal was 4.5 ± 1.22 and 4.83 ± 1.33 (p = 0.36) for deep and subpleural biopsies, respectively. The mean size of deep and subpleural biopsies was 1.758 ± 0.478 and 1.283 ± 0.851 cm(2), respectively (p = 0.0006). The mean weight of deep biopsies and subpleural biopsies was 0.156 ± 0.092 and 0.145 ± 0.047 mg, respectively (p = 0.83). No statistically significant difference was found between subpleural and deep biopsies regarding the mean quality scores of parenchyma-pleura (p = 0.36), vessels (p = 0.36), or bronchial tissue (p = 0.20). CONCLUSION: Both subpleural biopsies obtained during pleuroscopy and deep lung biopsy specimens obtained by electrocautery in animal subjects provided satisfactory material for histologic examination. Therefore, in DPLD, where the subpleural layers are involved, subpleural biopsies obtained during pleuroscopy might be sufficient for establishing an accurate diagnosis.

Sleepiness as a marker of glucose deregulation in obstructive sleep apnea.

BACKGROUND: Excessive daytime sleepiness (EDS) is a major but not universally present feature of obstructive sleep apnea syndrome (OSAS). The latter has been associated with glucose dysmetabolism and insulin resistance. The aim of this study was to examine the role of EDS by investigating potential differences between somnolent and non-somnolent OSAS patients in glucose metabolism, insulin resistance, and levels of cardiovascular risk factors. METHODS: Included were 25 newly diagnosed otherwise healthy OSAS patients, reporting EDS (ESS ≥ 11) and 25 age- and BMI-matched, non-somnolent (ESS ≤ 10) OSAS patients, who served as controls. Fasting glucose and insulin levels, as well as homeostatic model assessment of insulin resistance (HOMA(IR)) index, levels of hs-CRP, and lipidemic profile were measured. RESULTS: The two groups did not differ in anthropometric or sleep characteristics. A significant correlation of ESS with glucose (p = 0.004), insulin (p = 0.011), and HOMA(IR) (p = 0.031) was observed. Somnolent patients had higher levels of glucose (p = 0.045), insulin (p = 0.012), and HOMA(IR) (p = 0.027). No difference was detected in other markers between the two groups. CONCLUSIONS: Daytime sleepiness in OSAS patients is associated with hyperglycemia and hyperinsulinemia. These results suggest its potential use as a surrogate marker of insulin resistance in such patients.

Inflammation of the Pleural Cavity: A Review on Pathogenesis, Diagnosis and Implications in Tumor Pathophysiology.

Pleural effusions are a common respiratory condition with many etiologies. Nonmalignant etiologies explain most pleural effusions and despite being nonmalignant, they can be associated with poor survival; thus, it is important to understand their pathophysiology. Furthermore, diagnosing a benign pleural pathology always harbors the uncertainty of a false-negative diagnosis for physicians and pathologists, especially for the group of non-specific pleuritis. This review aims to present the role of the inflammation in the development of benign pleural effusions, with a special interest in their pathophysiology and their association with malignancy.

Pulmonary calcinosis associated with Alport syndrome.

We report the case of a 48-year-old woman under dialysis from chronic renal failure (CRF) since the age of 27, due to Alport syndrome. The patient underwent routine chest X-ray on which diffuse micronodules were shown. Chest computed tomography showed partially calcified micronodules with centrilobular distribution respecting the subpleural spaces and predominant in the upper lobar regions. Metastatic pulmonary calcinosis was confirmed by the bone scan with an overall course of 29 years. This is the first reported case of pulmonary calcinosis from CRF due to Alport syndrome.

Prognostic role of immune microenvironment in pleural metastases from breast and lung adenocarcinomas.

Background: Pleural metastatic disease is a common disease with dismal prognosis. The immune microenvironment of metastatic pleural tissue remains largely unknown. Thus, we aimed to investigate the presence of different immune cell populations, and to compare them with clinical characteristics. Methods: We included 70 patients with lung and breast adenocarcinoma (ADC) diagnosed with pleural metastasis during a 2-year period with the primary endpoint to investigate if the main immune cell populations are present in pleural metastases and if they have any prognostic role. Secondary endpoints were to detect any differences in their presence between lung and breast primaries and to search for any correlation with the macroscopic (thoracoscopic) findings. We used immunohistochemical techniques for the detection of CD4+, CD8+, CD20+, CD163+ and S100+ cells in whole tissue pleural biopsies of lung and breast metastases. Results: Primary endpoint: all these populations are present in the biopsies from lung and higher stromal and intratumoral CD4 counts, as well as higher stromal CD20 cells were positive prognostic factors for lung cancer metastases, while higher S100 intratumoral counts were positive prognostic factors in lung and marginally breast cancer metastases. Secondary endpoints: significant higher values for the stromal CD163 group (P=0.04) and for the intratumoral S100 group (P=0.006) were seen in lung compared to breast metastases. Interesting correlations were also noted between thoracoscopic findings (nodules, masses, pachypleuritis) and the different factors studied. Conclusions: Our data show that the immune microenvironment may be important in this advanced tumoral setting and that possible targets of the nowadays numerous treatment strategies implicating the immune system may merit further exploration in this poor prognosis disease.

New challenges in medical thoracoscopy.

Thoracoscopy is currently the gold standard for the diagnosis and treatment of pleural diseases. Its diagnostic yield is 95% in patients with malignant pleural disease, with approximately 90% successful pleurodesis for malignant pleural effusion and 95% for pneumothorax. At the same time, thoracoscopy constitutes an important tool in the research of pleural pathophysiology and molecular biology. The improvement of technology has provided important tools to thoracoscopy, such as autofluorescence, narrow band imaging, and infrared light, used in clinical and basic research in many disorders involving the pleura. For these reasons, training in thoracoscopy should be considered equally important as training in bronchoscopy for residents in respiratory medicine.

Intrapleural r-tPA in association with low-molecular heparin may cause massive hemothorax resulting in hypovolemia.

The use of intrapleural instillation of recombinant tissue plasminogen activator (r-tPA) in the treatment of pleural infection may increase pleural fluid drainage associated with a clinical and imaging improvement, leading to a faster resolution. The use of r-tPA is generally well tolerated. Here we report 2 cases of massive pleural hemorrhage resulting in life-threatening hypovolemia, in 2 patients treated with intrapleural r-tPA for a pleural infection, who were simultaneously receiving systemic anticoagulation (1 therapeutic, the second prophylactic) with low-molecular weight heparin. It appears that the decision of treating pleural infection with r-tPA in patients receiving therapeutic or prophylactic systemic anticoagulation must be well balanced and in case of association of these compounds, close monitoring is necessary.

The Immune Microenvironment of Malignant Pleural Mesothelioma: A Literature Review.

Malignant pleural mesothelioma (MPM) is a rare and aggressive tumour with a poor prognosis, associated with asbestos exposure. Nowadays, treatment is based on chemotherapy with a median overall survival of less than two years. This review highlights the main characteristics of the immune microenvironment in MPM with special emphasis on recent biological advances. The MPM microenvironment is highly infiltrated by tumour-associated macrophages, mainly M2-macrophages. In line with infiltration by M2-macrophages, which contribute to immune suppression, other effectors of innate immune response are deficient in MPM, such as dendritic cells or natural killer cells. On the other hand, tumour infiltrating lymphocytes (TILs) are also found in MPM, but CD4+ and CD8+ TILs might have decreased cytotoxic effects through T-regulators and high expression of immune checkpoints. Taken together, the immune microenvironment is particularly heterogeneous and can be considered as mainly immunotolerant or immunosuppressive. Therefore, identifying molecular vulnerabilities is particularly relevant to the improvement of patient outcomes and the assessment of promising treatment approaches.