Diagnosis and Treatment of Pleural Effusion. Recommendations of the Spanish Society of Pulmonology and Thoracic Surgery. Update 2022.

Pleural effusion (PE) is a common yet complex disease that requires specialized, multidisciplinary management. Recent advances, novel diagnostic techniques, and innovative patient-centered therapeutic proposals have prompted an update of the current guidelines. This document provides recommendations and protocols based on a critical review of the literature on the epidemiology, etiology, diagnosis, prognosis, and new therapeutic options in PE, and addresses some cost-effectiveness issues related to the main types of PE.

Pleural mesothelioma. / Mesotelioma pleural.

The diagnosis of diffuse pleural mesothelioma requires in most cases a pleural biopsy, performed either under imaging guidance (ultrasound or computed tomography) or thoracoscopy. Loss of BAP1 or MTAP expression (immunohistochemistry) and homozygous deletion of CDKN2A (fluorescence in situ hybridization) are the basic molecular markers for the diagnosis of mesothelioma. The histologic type and patient's performance status are the most important prognostic factors. Pleural effusion can be managed by the insertion of tunneled pleural catheters, either as a stand-alone measure (e.g., patients not amenable to multimodality therapy who have been diagnosed by pleural fluid cytology or image-guided biopsy) or combined with the administration of aerosolized talc during a diagnostic thoracoscopy. Immunotherapy is one of the front-line approaches in inoperable patients, particularly in biphasic or sarcomatous histologic varieties.

A prediction rule for estimating the risk of bacteremia in patients with community-acquired pneumonia.

BACKGROUND: We endeavored to construct a simple score based entirely on epidemiological and clinical variables that would stratify patients who require hospital admission because of community-acquired pneumonia into groups with a low or high risk of developing bacteremia. METHODS: Derivation and internal validation cohorts were obtained by retrospective analysis of a database that included 3116 consecutive patients with community-acquired pneumonia from 2 university hospitals. Potential predictive factors were determined by means of a multivariate logistic regression equation applied to a cohort consisting of 60% of the patients. Points were assigned to significant parameters to generate the score. It was then internally validated with the remaining 40% of patients and was externally validated using an independent multicenter cohort of 1369 patients. RESULTS: The overall rates of bacteremia were 12%-16% in the cohorts. The clinical probability estimate of developing bacteremia was based on 6 variables: liver disease, pleuritic pain, tachycardia, tachypnea, systolic hypotension, and absence of prior antibiotic treatment. For the score, 1 point was assigned to each predictive factor. In the derivation cohort, a cutoff score of 2 best identified the risk of bacteremia. In the validation cohorts, rates of bacteremia were <8% for patients with a score 1 (43%-49% of patients), whereas blood culture results were positive in 14%-63% of cases for patients with a score 2. CONCLUSIONS: This clinical score, based on readily available and objective variables, provides a useful tool to predict bacteremia. The score has been internally and externally validated and may be useful to guide diagnostic decisions for community-acquired pneumonia.

[Influence of pleural fluid red blood cell count on the misidentification of transudates]. / Influencia del recuento de hematíes del líquido pleural en la identificación errónea de los trasudados.

BACKGROUND AND OBJECTIVE: Light's criteria misclassify a quarter of transudates as exudates. We assessed the influence of red blood cell counts on pleural lactate dehydrogenase (LDH) levels and, thereby, on the specificity of Light's criteria. PATIENTS AND METHOD: We retrospectively reviewed 1,312 consecutive patients with pleural effusion, of whom 1,014 were exudates and 298 transudates according to clinical criteria. The relationship between pleural erythrocytes and LDH using simple linear regression analysis, as well as the operating characteristics of Light's criteria, were assessed. Finally, a formula to correct pleural LDH levels, according to the erythrocyte count, was generated. RESULTS: There was a linear relationship between the pleural erythrocyte count and LDH levels (r = 0.44; p < 0.001). Light's criteria yielded 81% specificity in patients with pleural erythrocyte counts < or = 10.000 3 10(6)/l, as compared to 61% in a group with a higher erythrocyte counts (p < 0.01). The application of the LDH formula enabled the correct reclassification of 24 of 64 (37%) false exudates. CONCLUSIONS: A high pleural erythrocyte count, through its influence on the LDH levels, may lead to a transudate being misclassified as an exudate after applying Light's criteria.

Diagnosis and Treatment of Pleural Effusion. Recommendations of the Spanish Society of Pulmonology and Thoracic Surgery. Update 2022

Pleural effusion (PE) is a common yet complex disease that requires specialized, multidisciplinary management. Recent advances, novel diagnostic techniques, and innovative patient-centered therapeutic proposals have prompted an update of the current guidelines. This document provides recommendations and protocols based on a critical review of the literature on the epidemiology, etiology, diagnosis, prognosis, and new therapeutic options in PE, and addresses some cost-effectiveness issues related to the main types of PE. (AU)

Soluble oncoprotein 185HER-2 in pleural fluid has limited usefulness for the diagnostic evaluation of malignant effusions.

OBJECTIVES: To investigate whether pleural levels of the soluble oncoprotein 185 HER-2 (sp185(HER-2)), individually or in combination with CEA and CA 15-3, were useful for the diagnosis of malignant effusions. DESIGN AND METHODS: Levels of CEA, CA 15-3, and sp185(HER-2) were measured in the pleural fluid from 135 malignant and 103 benign effusions. Thresholds of these tumor markers were chosen for a diagnostic specificity of >or=99%. RESULTS: Pleural sp185(HER-2) levels greater than 25 ng/mL were observed in 20% of breast and 10% of lung adenocarcinomas, and predicted a malignant effusion with a sensitivity of 7% and a likelihood ratio of 7.6. Combination of CEA and CA 15-3 resulted in 50% sensitivity, while adding sp185(HER-2) to this panel nonsignificantly increased sensitivity by 5% (P = 0.45). Only 1 patient with breast adenocarcinoma among 45 cytology-negative malignant effusions had sp185(HER-2) above the diagnostic cutoff point. CONCLUSION: Measurement of pleural fluid sp185(HER-2) has poor diagnostic performance in patients with malignant effusions.

Etiology and pleural fluid characteristics of large and massive effusions.

STUDY OBJECTIVE: To report the etiology of large and massive pleural effusions, and to compare their biochemical fluid characteristics with those of smaller size, and between malignant and nonmalignant conditions. DESIGN: Retrospective chart review of all patients undergoing thoracentesis at an academic medical center in Lleida, Spain, during a 10-year period. PATIENTS: Posteroanterior chest radiographs were available in 766 patients during the study period. Large pleural effusions (ie, two thirds or more of the hemithorax without its complete obliteration) were identified in 70 patients (9%), and massive pleural effusions (ie, hemithorax was completely opacified) were identified in 93 patients (12%). RESULTS: A similar etiologic spectrum between large and massive pleural effusions was observed. The most frequent cause of these pleural effusions was malignancy (89 patients; 55%), followed by complicated parapneumonic or empyema (36 patients; 22%), and tuberculosis (19 patients; 12%). Compared with nonmalignant pleural effusions, patients with large or massive malignant pleural effusions were more likely to have pleural fluids with higher RBC counts (18.0 x 10(9) cells/L vs 2.7 x 10(9) cells/L, respectively; p < 0.001) and lower adenosine deaminase (ADA) activity (11.5 vs 31.5 U/L, respectively; p < 0.001), which were the two parameters that were selected by a stepwise logistic-regression model as independent predictors of malignancy. In addition, large/massive malignant pleural effusions showed higher median RBC counts (18.0 x 10(9) cells/L vs 4.3 x 10(9) cells/L, respectively; p < 0.001), higher lactate dehydrogenase levels (641 vs 409 U/L, respectively; p = 0.001), lower pH (7.39 vs 7.42, respectively; p = 0.006) content, but similar cytologic yield (63% vs 53%, respectively; p = 0.171) than smaller malignant pleural effusions. CONCLUSIONS: The presence of a large or massive pleural effusion enables the clinician to narrow the differential diagnosis of pleurisy, since most effusions are secondary to malignancy or infections (either bacterial or mycobacterial). Bloody pleural fluid with low ADA content favors a malignant condition.

Tumor necrosis factor-alpha in pleural fluid: a marker of complicated parapneumonic effusions.

STUDY OBJECTIVES: We sought to determine whether pleural fluid tumor necrosis factor (TNF)-alpha is a more accurate parameter to identify nonpurulent complicated parapneumonic effusion (CPPE) than the classical chemistries, namely pH, glucose, or lactate dehydrogenase (LDH). METHODS: We studied 80 consecutive patients with parapneumonic effusions (35 with uncomplicated parapneumonic effusion [UPPE], 23 with nonpurulent CPPE, and 22 with empyema). Concentrations of standard biochemical parameters together with TNF-alpha were measured in pleural fluid, the latter by using an immunoenzymometric assay. RESULTS: Pleural TNF-alpha was significantly higher in CPPE (133.0 pg/mL) and empyema (142.2 pg/mL) than in UPPE (39.1 pg/mL). A cut-off value of 80 pg/mL for pleural TNF-alpha resulted in a sensitivity, specificity, and area under receiver operating characteristic curve (AUC) of 78%, 89%, and 0.87, respectively, for the diagnosis of nonpurulent CPPE. A multivariate analysis selected both pleural TNF-alpha > or = 80 pg/mL and LDH > or = 1,000 U/L (sensitivity, 74%; AUC = 0.86), but excluded pleural glucose < or = 60 mg/dL (sensitivity, 39%; AUC = 0.82) and pH < or = 7.20 (sensitivity, 41%; AUC = 0.78), for identifying the need for drainage. The combined sensitivity of pleural fluid TNF-alpha and LDH was found to be 91%. CONCLUSIONS: Pleural TNF-alpha may contribute to the identification of patients with nonpurulent CPPE with at least the same diagnostic accuracy, if not better, than the use of pH, glucose, or LDH.

Use of a panel of tumor markers (carcinoembryonic antigen, cancer antigen 125, carbohydrate antigen 15-3, and cytokeratin 19 fragments) in pleural fluid for the differential diagnosis of benign and malignant effusions.

STUDY OBJECTIVE: The diagnostic value of tumor markers in pleural fluid is subject to debate. The aim of this study was to evaluate the diagnostic performance of several tumor markers in common use for detecting malignant pleural disease. DESIGN: Blinded comparison of four tumor markers in pleural fluid with a confirmatory diagnosis of malignancy by pleural cytology or thoracoscopic biopsy. SETTING: Two teaching hospitals in Spain. PATIENTS AND METHODS: A total of 416 patients (166 with definite malignant effusions, 77 with probable malignant effusions, and 173 with benign effusions) were enrolled. Among them, there were 42 patients recruited from one of the participant centers with thoracoscopic facilities, who had false-negative fluid cytology findings and malignancy confirmed by medical thoracoscopy. Tumor markers in pleural fluid were determined either by electrochemiluminescence immunoassay (carcinoembryonic antigen [CEA], carbohydrate antigen 15-3 [CA 15-3], cytokeratin 19 fragments [CYFRA 21-1]) or microparticle enzyme immunoassay (cancer antigen 125 [CA 125]) technologies. Cutoff points that yielded 100% specificity (ie, all patients with benign effusions had levels below this cutoff) were selected for each marker. RESULTS: Malignant pleural effusions (PEs) had higher levels of pleural fluid markers than did effusions due to benign conditions. At 100% specificity, a pleural CEA > 50 ng/mL, CA 125 > 2,800 U/mL, CA 15-3 > 75 U/mL, and CYFRA 21-1 > 175 ng/mL had 29%, 17%, 30%, and 22% overall sensitivities, respectively. The combination of the four tumor markers reached 54% sensitivity, whereas the combined use of the cytology and the tumor marker panel increased the diagnostic yield of the former by 18% (95% confidence interval, 13 to 23%). More than one third of cytology-negative malignant PEs could be identified by at least one marker of the panel. CONCLUSIONS: No single pleural fluid marker seems to be accurate enough as to be introduced in the routine workup of PE diagnosis. However, a tumor marker panel may represent a helpful adjunct to cytology in order to rule in malignancy as a probable diagnosis, thus guiding the selection of patients who might benefit from further invasive procedures.

Evaluation of the polymerase chain reaction method for detection of Streptococcus pneumoniae DNA in pleural fluid samples.

STUDY OBJECTIVE: Streptococcus pneumoniae is the most frequent causative agent of community-acquired pneumonia (CAP); however, an etiologic diagnosis by traditional techniques can be accomplished in only a small percentage of patients with CAP. Pleural fluid is present in approximately 40% of patients with CAP; therefore, we hypothesized that detection of S pneumoniae DNA in pleural fluid by polymerase chain reaction (PCR) may help to increase the rate of diagnosis of pneumococcal pneumonia. DESIGN: A prospective study of cases. SETTING: A university hospital in Lleida, Spain. PATIENTS AND METHODS: One hundred two samples of pleural fluid (51 samples from consecutive adult patients with pneumonia and 51 samples from unselected control subjects) were tested by the nested-PCR method to detect selected pneumolysin gene of S pneumoniae, and the results were compared with those provided by alternative diagnostic methods. RESULTS: PCR in pleural fluid had a diagnostic sensitivity of 78% in patients with pneumococcal pneumonia, with positive results in 2 of 2 patients (100%) and 5 of 7 patients (71%) who had positive or negative pleural fluid culture findings, respectively. PCR results were also positive in 3 of 24 patients (12%) with pneumonia of unknown etiology and negative in all patients with pneumonia due to microorganisms other than S pneumoniae. Thus, the calculated specificity was 93%. Among control subjects, PCR gave positive results in two cases (4%). CONCLUSION: The nested-PCR test, applied to pleural fluid samples from patients with CAP, showed a sensitivity of 78% and a specificity of 93% in the diagnosis of pneumococcal pneumonia.

Mesotelioma pleural / Pleural mesothelioma

El diagnóstico de mesotelioma pleural difuso requiere en la mayoría de los casos una biopsia pleural, realizada bajo control de imagen (ecografía o tomografía computarizada) o mediante toracoscopia. La pérdida de expresión de BAP1 o de MTAP (inmunohistoquímica) y la deleción homocigota de CDKN2A (hibridación fluorescente in situ) constituyen los marcadores moleculares básicos para el diagnóstico de mesotelioma. El tipo histológico y el estado funcional del paciente son los factores pronósticos más importantes. El control del derrame pleural se puede realizar a través de la inserción de catéteres pleurales tunelizados, bien como medida aislada (p. ej. pacientes no susceptibles de terapia multimodal que se han diagnosticado por citología del líquido pleural o biopsia guiada por imagen) o combinada con la administración de talco aerosolizado durante una toracoscopia diagnóstica. La inmunoterapia constituye una de las primeras líneas de tratamiento en pacientes inoperables, particularmente en las variedades histológicas bifásicas o sarcomatosas. (AU)

The diagnosis of diffuse pleural mesothelioma requires in most cases a pleural biopsy, performed either under imaging guidance (ultrasound or computed tomography) or thoracoscopy. Loss of BAP1 or MTAP expression (immunohistochemistry) and homozygous deletion of CDKN2A (fluorescence in situ hybridization) are the basic molecular markers for the diagnosis of mesothelioma. The histologic type and patient's performance status are the most important prognostic factors. Pleural effusion can be managed by the insertion of tunneled pleural catheters, either as a stand-alone measure (e.g., patients not amenable to multimodality therapy who have been diagnosed by pleural fluid cytology or image-guided biopsy) or combined with the administration of aerosolized talc during a diagnostic thoracoscopy. Immunotherapy is one of the front-line approaches in inoperable patients, particularly in biphasic or sarcomatous histologic varieties. (AU)

Core competencies in internal medicine.

The working group on Competencies of Internal Medicine from the Spanish Society of Internal Medicine (SEMI) proposes a series of core competencies that we consider should be common to all European internal medicine specialists. The competencies include aspects related to patient care, clinical knowledge, technical skills, communication skills, professionalism, cost-awareness in medical care and academic activities. The proposal could be used as a working document for the Internal Medicine core curriculum in the context of the educational framework of medical specialties in Europe.