Visceral Leishmaniasis Masquerading as Drug-Induced Pancytopenia in Lung Cancer Patients.

Maintenance chemotherapy is a standard treatment in patients with non-progressive advance staged IV non-squamous non-small cell lung cancer after induction therapy. Here, we report the case of a 53-year-old man undergoing a maintenance monotherapy with pemetrexed who presented prolonged pancytopenia despite filgrastim injections. A bone marrow aspiration revealed a macrophage activation syndrome with Leishmania amastigotes. A Polymerase Chest Reaction testing confirmed the diagnosis of visceral leishmaniasis. Treatment with liposomal amphotericin B was started. Oncologists should bear in mind that visceral leishmaniasis in endemic areas can potentially induce severe and prolonged pancytopenia in immunosuppressed patients, during chemotherapy in particular.

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.

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.

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.

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.

A new hybrid immunocapture bioassay with improved reproducibility to measure tissue factor-dependent procoagulant activity of microvesicles from body fluids.

BACKGROUND: The procoagulant activity of tissue factor-bearing microvesicles (MV-TF) has been associated with the risk of developing venous thrombosis in cancer patients. However, MV-TF assays are limited either by i) a lack of specificity, ii) a low sensitivity, or iii) a lack of repeatability when high-speed centrifugation (HS-C) is used to isolate MV. Therefore, our objective was to develop a new hybrid "capture-bioassay" with improved reproducibility combining MV immunocapture from biofluids and measurement of their TF activity. MATERIALS AND METHODS: Factor Xa generation and flow cytometry assays were used to evaluate IMS beads performance, and to select the most effective capture antibodies. The analytical performance between IMS-based and HS-C-based assays was evaluated with various models of plasma samples (from LPS-activated blood, spiked with tumoral MV, or with saliva MV) and different biofluids (buffer, plasma, saliva, and pleural fluid). RESULTS: Combining both CD29 and CD59 antibodies on IMS beads was as efficient as HS-C to isolate plasmatic PS+ MV. The IMS-based strategy gave significantly higher levels of MV-TF activity than HS-C in tumor MV spiked buffer, and both pleural fluids and saliva samples. Surprisingly, lower TF values were measured in plasma due to TFPI (TF pathway inhibitor) non-specifically adsorbed onto beads. This was overcome by adding a TFPI-blocking antibody. After optimization, the new IMS-based assay significantly improved reproducibility of MV-TF bioassay versus the HS-C-based assay without losing specificity and sensitivity. In addition, this approach could identify the cellular origin of MV-TF in various biological fluids. CONCLUSION: Compared to HS-C, the IMS-based measurement of MV-TF activity in body fluids improves reproducibility and makes the assay compatible with clinical practice. It can facilitate future automation.

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.

Impact of Silicone Stent Placement in Symptomatic Airway Obstruction due to Non-Small Cell Lung Cancer - A French Multicenter Randomized Controlled Study: The SPOC Trial.

BACKGROUND: Therapeutic bronchoscopy (TB) is an accepted strategy for the symptomatic management of central airway malignant obstruction. Stent insertion is recommended in case of extrinsic compression, but its value in preventing airway re-obstruction after endobronchial treatment without extrinsic compression is unknown. OBJECTIVE: Silicone stent Placement in symptomatic airway Obstruction due to non-small cell lung Cancer (SPOC) is the first randomized controlled trial investigating the potential benefit of silicone stent insertion after successful TB in symptomatic malignant airway obstruction without extrinsic compression. METHOD: We planned an inclusion of 170 patients in each group (stent or no stent) over a period of 3 years with 1-year follow-up. The 1-year survival rate without symptomatic local recurrence was the main endpoint. Recurrence rate, survival, quality of life, and stent tolerance were secondary endpoints. During 1-year follow-up, clinical events were monitored by flexible bronchoscopies and were evaluated by an independent expert committee. RESULTS: Seventy-eight patients (mean age 65 years) were randomized into 2 arms: stents (n = 40) or no stents (n = 38) after IB. Consequently, our main endpoint could not be statistically answered. Improvement of dyspnea symptoms is noticeable in each group but lasts longer in the stent group. Stents do not change the survival curve but reduce unattended bronchoscopies. In the no stent group, 19 new TB were performed with 16 stents inserted contrasting with 10 rigid bronchoscopies and 3 stents placed in the stent group. In a subgroup analysis according to the oncologic management protocol following TB (first-line treatment and other lines or palliation), the beneficial effect of stenting on obstruction recurrence was highly significant (p < 0.002), but was not observed in the naïve group, free from first-line chemotherapy. CONCLUSION: Silicone stent placement maintains the benefit of TB after 1 year on dyspnea score, obstruction's recurrence, and the need for new TB. Stenting does not affect the quality of life and is suggested for patients after failure of first-line chemotherapy. It is not suggested in patients without previous oncologic treatment.

Novel pleural-bladder pump in malignant pleural effusions: from animal model to man.

Malignant pleural effusion is common and causes disabling symptoms such as breathlessness. Treatments are palliative and centred around improving symptoms and quality of life but an optimal management strategy is yet to be universally agreed. A novel pump system, allowing fluid to be moved from the pleural space to the urinary bladder, may have a role for the management of recurrent malignant pleural effusion. We hereby describe the first animal study using this device and the results of the first application in patients.

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.

Lateral decubitus chest radiography or chest ultrasound to predict pleural adhesions before medical thoracoscopy: a prospective study.

BACKGROUND: Medical thoracoscopy (MT) is the gold-standard to investigate unexplained pleural exudates. However, the major prerequisite is an easy pleural access obtained by creating an artificial pneumothorax at the beginning of the procedure which can be a challenge in case of pleural adhesions and make the procedure unsafe. The detection of pleural adhesions prior to MT is necessary. Nowadays chest ultrasonography (CUS) is considered the best procedure to detect pleural adhesions. However, this technique is not available in all countries where the assessment of the pleural cavity is only based on chest radiography. Therefore, we conducted this study to compare the performance of lateral decubitus chest radiography (LDCR) and CUS to predict pleural adhesions. METHODS: LDCR and CUS were performed prior MT in consecutive patients presenting exudative pleural effusion to detect pleural adhesions. The diagnostic sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy for each pre thoracoscopy procedure were calculated. RESULTS: Data analysis for the sixty-six enrolled patients showed a higher superiority to detect pleural adhesions for CUS in comparison to LDCR for all the parameters analyzed. CONCLUSIONS: These results confirm that pre-MT CUS is the cornerstone to evaluate the access to the pleural cavity and justify educational program in this field in all centers which intends to develop interventional pulmonology.

Anaplastic thyroid carcinoma mimicking a malignant pleural mesothelioma: Clues for diagnosis.

Pleural metastasis of thyroid carcinoma is very rarely encountered in the evaluation of pleural effusion and diagnosis may be challenging. However, an anaplastic transformation of papillary thyroid carcinoma (PTC), although a rare condition, should be considered even after a prolonged period of patient follow-up. Here we report a case of anaplastic thyroid carcinoma mimicking malignant pleural mesothelioma diagnosed nine years after the initial diagnosis of PTC and detail the clues used to orient and confirm the diagnosis.

Recent developments in pleurodesis for malignant pleural disease.

OBJECTIVE: Metastatic pleural effusion (MPE) is one of the most frequent causes of pleural effusion. The aims of the therapeutic management are palliation of symptoms and improvement in patient's quality of life. The first step is a therapeutic thoracentesis. In case of a recurrent MPE, pleural maneuvers can be used to manage symptoms based on either ambulatory pleural drainage or pleurodesis to prevent fluid accumulation. The aim of this review is to describe recent advances, according to the best available evidence, in the field of pleurodesis for the management of MPE. DATA SOURCE AND STUDY SELECTION: Three different searches of the most clinically relevant articles and up-to-date results in the field of pleurodesis for the management of MPE were performed using PubMed. Different indexing terms and time restriction were chosen. From these PubMed searches, 322 articles were respectively found. After cross-checking these three lists and the selection of articles published after January 2010 specially dedicated to the management of MPE by pleurodesis, the abstracts of 106 articles were extracted to feed the corpus of this review. RESULTS AND CONCLUSION: Treatment approaches of recurrent MPE should take into account multiple factors in particular patient's life expectancy and preference. If talc is the best sclerosing agent alone or in combination with indwelling pleural catheter which is a promising strategy, the pathophysiology of MPE has to be revisited in order to propose a personalized management targeting intrapleural key molecules involved in the genesis of malignant process.

Chest ultrasonography to assess the kinetics and efficacy of talc pleurodesis in a model of pneumothorax: an experimental animal study.

Talc pleurodesis is used to avoid recurrences in malignant pleural effusions or pneumothorax. The lack of lung sliding detected by chest ultrasonography (CUS) after talc application is indicative of the effectiveness of pleurodesis. The objective of our study was to explore, in an animal model, the capacity of CUS to predict the quality of a symphysis induced by talc poudrage (TP) and talc slurry (TS). We induced an artificial pneumothorax in six healthy pigs prior to talc application. TP was performed on one hemithorax, followed by TS on the other side 1 week later. 108 points on the chest were marked and evaluated by ultrasonography during the study. TP showed higher sonographic scores compared to TS starting from 72 h after talc administration. At autopsy, a higher grade of symphysis was observed for TP, and a high correlation rate was registered between CUS and macroscopic findings. Histological analysis also showed a higher grade of pleural symphysis for TP. CUS is a reliable tool to assess talc pleurodesis. The quality and kinetics of the pleural symphysis are also evaluable by ultrasonography. Pleurodesis by TP is more effective than TS in this experimental model of pneumothorax.

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.

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.

Positive pleural cytology is an indicator for visceral pleural invasion in metastatic pleural effusions.

INTRODUCTION: In case of undiagnosed pleural effusions, it is necessary to conduct thoracentesis with pleural fluid (PF) cytology. Yet, sensitivity of PF cytology is widely variable as a result of sample size, experience, and preparation method. OBJECTIVES: The aim of this study was to assess whether pleural fluid (PF) cytology is correlated to visceral or parietal pleural invasion as assessed by thoracoscopy in metastatic pleural effusions. METHODS: All records of patients with pleural effusion were reviewed. The inclusion criteria were as follows: PF cytology, reported appearance of macroscopic pleural invasion during thoracoscopy and malignant diagnosis. Patients with mesothelioma were excluded. Finally, 287 patients who met all criteria were selected. According to the thoracoscopy findings, the extent of the disease on the pleura was analyzed in relation to the PF cytology. RESULTS: In this study, 160 patients (55.7%) had a positive PF cytology (Group A) while 127 (44.3%) recorded negative PF cytology (Group B). From Group A, patients with visceral pleural invasion were 120 (75%) while only 49 patients (38.5%) were found from Group B and the difference was statistically significant (P < .00001). In univariate analysis, visceral pleural invasion was strongly associated with positive PF cytology (P < .001). Other significant associations with positive PF cytology included PF bloody aspect (P = .012), and endoscopic mixed pattern of pleural invasion (P = .0039). Only visceral pleural invasion was statistically significant in multivariate analysis (P < .001). CONCLUSIONS: In patients with pleural metastatic disease, visceral pleural invasion is the only significant factor associated with positive pleural fluid cytology.

Low lamin A expression in lung adenocarcinoma cells from pleural effusions is a pejorative factor associated with high number of metastatic sites and poor Performance status.

The type V intermediate filament lamins are the principal components of the nuclear matrix, including the nuclear lamina. Lamins are divided into A-type and B-type, which are encoded by three genes, LMNA, LMNB1, and LMNB2. The alternative splicing of LMNA produces two major A-type lamins, lamin A and lamin C. Previous studies have suggested that lamins are involved in cancer development and progression. A-type lamins have been proposed as biomarkers for cancer diagnosis, prognosis, and/or follow-up. The aim of the present study was to investigate lamins in cancer cells from metastatic pleural effusions using immunofluorescence, western blotting, and flow cytometry. In a sub-group of lung adenocarcinomas, we found reduced expression of lamin A but not of lamin C. The reduction in lamin A expression was correlated with the loss of epithelial membrane antigen (EMA)/MUC-1, an epithelial marker that is involved in the epithelial to mesenchymal transition (EMT). Finally, the lamin A expression was inversely correlated with the number of metastatic sites and the WHO Performance status, and association of pleural, bone and lung metastatic localizations was more frequent when lamin A expression was reduced. In conclusion, low lamin A but not lamin C expression in pleural metastatic cells could represent a major actor in the development of metastasis, associated with EMT and could account for a pejorative factor correlated with a poor Performance status.