Pleural Effusion Of Unknown Origin Research Articles

Дифференциальная диагностика плеврального выпота при молекулярном скрининге генов SHOX2, DAPK1, RAR-beta и miR-375

At the Federal Scientific and Clinical Center of the Federal Medical and Biological Agency of Russia, an analysis of 62 patients with cancer pathology and other pathologies complicated by hydrothorax was performed. Method: methylation of SHOX2, DAPK1, RAR-beta and miR-375 genes using methyl-sensitive PCR. The development of the oncological process is accompanied by genetic polymorphism of genes, including SHOX2, DAPK1, RAR-beta and miR-375. The possibility of predicting oncological pathology and facilitating the search for the primary source of the oncological process in patients with pleural effusion of unknown origin through the study of the studied genes was revealed. Using the MedCalc version 12.3.0.0 program, 3 reliable systems of cancer markers were obtained for methylation of genes of a group of genes: the first is SHOX2, miR-375 (sensitivity — 62.0%, specificity — 82.0%), the second is SHOX2 + miR-375 + DAPK1 (65.0 and 76.0%, respectively), the third is SHOX2 + RAR-beta + miR-375 + DAPK1 (36.0 and 94.0%, respectively). It is advisable to conduct a genetic study of pleural fluids in patients with hydrothorax of unknown etiology.

Equine multinodular pulmonary fibrosis and presumed corticosteroid‐induced side effects in a horse

SummaryEquine multinodular pulmonary fibrosis (EMPF) associated with herpesvirus‐5 infection (EHV‐5), is a severe, fibrosing interstitial lung disease of horses. Most common reported clinical signs are pyrexia, weight loss, depression, respiratory distress with tachypnoea and cough. Multiple tissue tropism of the EHV‐5 has been suggested. Treatment with valacyclovir and corticosteroids has been reported to be successful in a few cases, but the disease is usually associated with a poor prognosis because of progressive impairment of respiratory function. Corticosteroid administration can carry potential side effects, such as hypothalamic–pituitary–adrenal axis suppression, laminitis and increased susceptibility to infections. This report described a case of an 11‐year‐old gelding diagnosed with EMPF. The horse was treated with valacyclovir and corticosteroids and, after a transient initial improvement, showed a rapid deterioration of clinical signs and multiple complications, including severe bacterial dermatitis, liver damage and pleural effusion of unknown origin. A polymerase chain reaction (PCR) assay of liver biopsy sample was positive for EHV‐5, confirming the virus' multiple tissue tropism. A role of corticosteroids in exacerbating the disease progression and the increasing susceptibility to infections was strongly suspected.

Pleurapunktion – Schritt für Schritt

Bei Pleuraergüssen unklarer Ursache sowie bei parapneumonischen Ergüssen ist die Pleurapunktion (Synonym: Thorakozentese, engl. thoracentesis) praktisch immer indiziert. Die Analyse des Punktats ist dabei wegweisend und bestimmt das weitere Management. Die Pleurapunktion ist in der Regel ein diagnostisch wertvoller und komplikationsarmer Eingriff – wenn man einige Grundsätze beachtet.

Pleurapunktion – Schritt für Schritt

Pleural effusions of unknown origin and parapneumonic effusions almost invariably require thoracentesis. Fluid analysis is fundamental and guides further diagnostic and therapeutic decisions. Thoracentesis yields high diagnostic value and is a generally safe procedure - given that some basic principles are considered.

Diagnosing malignant pleural effusion using clinical and analytical parameters.

Malignant pleural effusion (MPE) is common and diagnosis is often problematic. A cancer ratio (serum lactate dehydrogenases: pleural adenosine deaminase ratio) has been proposed for diagnosing MPE. However, the usefulness of this "cancer ratio" and the clinical-radiological criteria for diagnosing MPE has not been clearly determined to date. The aim of this study was to assess the performance of those parameters in the diagnosis of MPE. We analyzed 240 patients including 120 with MPE and 120 with non-MPE (93 tuberculous and 27 parapneumonic). Patients were divided into two groups: MPE and non-MPE (eg, tuberculous and parapneumonic). We constructed two predictive models to assess the probability of MPE: (a) clinical-radiological data only and (b) a combination of clinical-radiological data, the cancer ratio, and the carcinoembryonic antigen (CEA). The performances of the predictive models were assessed using receiver operating characteristic (ROC) curves and by examining the calibration. The area under the ROC curves for model 1 and model 2 were excellent, 0.936 and 0.998, respectively. The overall diagnostic accuracies for model 1 and model 2 were 87.5% and 98.8%, respectively. The results confirm that both models achieved a high diagnostic accuracy for MPE; however, model 2 was superior with the addition of its simplicity of use in daily practice. This model should be applied to determine which patients with a pleural effusion of unknown origin would not benefit from further invasive procedures.

Thoracentesis - Step by Step

Pleural effusions of unknown origin and parapneumonic effusions almost invariably require thoracentesis. Fluid analysis is fundamental and guides further diagnostic and therapeutic decisions. Thoracentesis yields high diagnostic value and is a generally safe procedure - given that some basic principles are considered.

胸腔穿刺により確定診断が得られなかった胸膜炎症例に対するSemi-flexible Thoracoscopyを用いた局所麻酔下胸腔鏡検査の有用性

胸腔穿刺により確定診断が得られなかった胸膜炎症例に対するSemi-flexible Thoracoscopyを用いた局所麻酔下胸腔鏡検査の有用性

원인불명의 고열 및 흉수 이후 악화된 폐결핵후유증 소양인환자 치험 1례 보고

Objectives It is important to care aftereffects of the tuberculosis such as cough and sputum especially for the old. The purpose of this study is to report a case which showed symptoms improvement after treatment with Hyungbangjihwang-tang.Methods To evaluate the results of this treatment, Decrease of cough and sputum was assessed by Visual Analogue Scale(VAS). The patient`s oral intake and body weight were measured.Results The patient who suffered with cough and sputum after tuberculosis developed high fever and pleural effusion of unknown origin. After treatment with western and oriental medicine, high fever and pleural effusion were subsided but cough and sputum got worse and body weight was decreased after high fever and pleural effusion. So we prescribed Hyungbangjihwang-tang and then the symptoms of the patient were improved.Conclusions This study suggests that using Sasang constitutuional medical treatment is effective for Soyangin patient with afftereffects of the tuberculosis such as cough and sputum.

Feasibility and safety of parietal pleural cryobiopsy during semi-rigid thoracoscopy.

Performing pleural biopsies during semi-rigid thoracoscopy is sometimes a difficult and time-consuming task because of the lack of mechanical power of dedicated flexible forceps in patients with thickened pleura. The purpose of this first ever pilot study was to test the feasibility of taking biopsy specimens by cryoprobe from the parietal pleura during semi-rigid thoracoscopy. Our aim was also to assess the diagnostic value and quality of specimens obtained, morphological features, feasibility of immunohistochemistry staining and possibility of DNA isolation. The secondary aim was to evaluate safety, tolerability and duration of the procedure. Fifteen patients with pleural effusion of unknown origin that underwent semi-rigid thoracoscopy were included. Biopsies were obtained using a flexible autoclavable cryoprobe 20416-032 (Erbokryo CA, ERBE, Tübingen, Germany) 2.4 mm in diameter and a semi-rigid autoclavable Olympus LTF-160 (Olympus, Tokyo, Japan) thoracoscope. Tissue samples were obtained from 14 patients (93.3%), three from each. Of the samples, 81% were easily interpretable and 19% were interpretable with some difficulty by the pathologist. The samples were of good quality, with the level of artifacts below 25%. The specimens were adequate for histological diagnosis, immunohistochemical staining and DNA isolation. There were no moderate or major bleeding problems after the biopsies; two patients experienced pain. The median duration of three cryobiopsies (per patient) was 4 min (range 3-6 min). Cryobiopsy during semi-rigid thoracoscopy appears worth to be evaluated in a larger prospective multicenter trial as our preliminary data were promising for efficacy and safety.

Semirigid thoracoscopy: an effective method for diagnosing pleural malignancies

BackgroundThoracoscopy with a semirigid instrument is a recent technique for diagnosing pleural diseases. The purpose of this study was to report diagnostic yield and complications of the method.Patients and methods.Patients with pleural effusion of unknown origin and/or pleural irregularities suspicious for pleural malignancy were included after less invasive means of diagnosis had failed. All procedures were performed under local anaesthesia with intravenous sedation/analgesia with a single point of entry with a semirigid thoracoscope (Olympus LTF-160). Data were collected prospectively between 2008 and 2012.ResultsOne hundred fifteen thoracoscopies were performed on 111 patients. The median age was 65 years (range 28–86 years), 14.4% were female and 85.6% male. Seventy-three (65.8%) patients had malignant pleural disease (malignant mesothelioma, metastatic cancer) and 38 (34.2%) had benign disease. The sensitivity, negative predictive value, and accuracy of the procedure for malignancy were 96.0%, 93.0%, and 97.4% respectively. Pleurodesis was carried out in 34 patients; in 32 (94.1%) it was assessed as successful after 1 month. There were 24 adverse events: three empyemas/pleural infections, three bronchopleural fistulae after chest tube placement and lung re-expansion, five patients had excessive pain after pleurodesis, six patients had sedation-associated hypotension, and seven patients had self-limited fever after plerodesis. One patient died 11 days after a procedure for advanced carcinoma.ConclusionsSemirigid thoracoscopy is an accurate and safe method for evaluation of pleural diseases and useful for therapeutic talc pleurodesis.

Rigid versus semi‐rigid thoracoscopy for the diagnosis of pleural disease: A randomized pilot study

Thoracoscopy with a semi-rigid instrument is a recent technique successfully used for diagnosing pleural diseases. However, there are concerns about the diagnostic adequacy of biopsy samples obtained by semi-rigid procedures when compared with rigid thoracoscopy. The purpose of this study was to compare the size, quality and diagnostic adequacy of biopsy specimens obtained at semi-rigid and rigid thoracoscopy in a prospective, randomized fashion. Patients with pleural effusion of unknown origin and/or pleural irregularities suspicious for pleural malignancy were included after less invasive means of diagnosis had failed. All procedures were performed under local anaesthesia with intravenous sedation/analgesia with a single point of entry. Patients were randomly assigned to a rigid instrument procedure (Olympus EndoEYE WA50120A, forceps) or semi-rigid instrument procedure (Olympus LTF-160, FB-55CR-1 forceps). Eighty-four patients were randomized. Five of them were excluded because of lack of pleural space. Thirty-eight patients were assigned to a rigid and 41 to a semi-rigid procedure, with mean follow up 24.1 (±8.1) months after the procedure. The average size of the sample obtained by rigid thoracoscopy was 24.7 mm(2) (±12.9), and 11.7 mm(2) (±7.6) by semi-rigid thoracoscopy. There were no differences in the quality and interpretability of the specimens assessed by the pathologist. The diagnostic accuracy was 100% for the rigid procedure and 97.6% for the semi-rigid procedure. The samples obtained by semi-rigid thoracoscopy were smaller, but of adequate quality. The diagnostic accuracy was comparable with that of rigid thoracoscopy in the evaluation of pleural disease.

Atrial standstill in a patient with progressive severe heart failure

Atrial standstill (AS) is a very rare condition characterized by complete loss of electrical and mechanical activity and excitability of the atria. Absence of P waves, bradycardia and junctional escape rhythm may suggest AS on surface ECG. In nearly half of the reported cases, the condition manifested with syncope [1, 2]. AS must be differentiated from common sinus node disease with sinus arrest or highgrade sinoatrial block that may have similar symptoms and surface ECG presentation [3]. AS has been rarely described to be primary with familial clustering and/or associated cardiac ion channel mutations [2, 4]. More commonly, it has been linked to heart disorders such as myocarditis, ischemic heart disease, or dilated cardiomyopathy [5–7]. AS occurring in the context of structural myocardial disease may indicate a poor prognosis [1, 8]. A 48-year-old female patient was referred to our emergency department due to fatigue, progressive dyspnoea on exertion and recurring syncope since a few months. Three years earlier she had presented to our outpatient clinic for recurrent pulmonary infections, where a normal ECG had been registered (Fig. 1a). Four months before she had been hospitalized at an external institution for ascites and pleural effusion of unknown origin and atrial fibrillation was diagnosed on surface ECG. A diuretic as well as oral anticoagulation were initiated. At presentation, the patient reported no family history of syncope or sudden death, and physical examination revealed cachexia (BMI 18.6 kg/m), but no obvious cardiopulmonary pathologies. Shortly after admission, the patient exhibited rapid polymorphic ventricular tachycardia (VT), requiring CPR and defibrillation. Twelve-lead surface ECG, recorded prior the arrhythmic event, showed absence of P waves with an escape rhythm of 48/min, a QRS duration of 70 ms, constant R–R intervals, and a prolonged QT interval of 600 ms (QTc 536 ms) (Fig. 1b). Laboratory findings revealed mild hypokalemia (3.2 mmol/ L), slightly elevated liver enzymes, an INR value of 2.1, N-terminal pro-BNP of 1,465 pg/mL (7.39 of normal value) and an ANP of 2.89 nmol/L (1.59 of normal value), whereas normal values were found for calcium, blood cell count, CRP, renal and thyroid functional parameters and CK. Chest X-ray revealed marked cardiomegaly, and the echocardiogram showed a dilated left ventricle with a severely reduced left ventricular ejection fraction (LVEF) of 20 %. Of note, LVEF had been reported to be 45 and 60 %, 2 and 3 months earlier, respectively. Furthermore, echocardiography showed dilated right and left atria along with moderate to severe tricuspid and moderate mitral regurgitation. A transesophageal echocardiogram revealed a thrombus in the left atrial appendage, where no significant flow was identifiable with Doppler imaging (Fig. 1c, d). Few hours after admission, the patient again developed recurrent polymorphic VT with syncope and need for defibrillation despite normalization of potassium levels (Fig. 1e). Coronary artery disease was ruled out angiographically and a temporary transvenous pacemaker was inserted. Myocardial biopsies were taken from the right ventricle, but provided no evidence for acute myocarditis [9], arrhythmogenic right ventricular dysplasia [10], amyloidosis or hemosiderosis. This was in line with findings from cardiac MRI, so that idiopathic dilated cardiomyopathy was diagnosed. With ventricular overdrive pacing at 80 bpm and initiation of beta-blocker medication VT did M. R. Schroeter (&) G. Hasenfus M. Zabel D. Vollmann Abt. Kardiologie und Pneumologie, Universitatsmedizin Gottingen, Herzzentrum, Robert-Koch-Str. 40, 37099 Gottingen, Germany e-mail: mschroeter@med.uni-goettingen.de

Pregnancy and labour in a woman with left-side pleural effusion of unknown origin

Pregnancy and labour in a woman with left-side pleural effusion of unknown origin

Pleural Effusions from Congestive Heart Failure

In heart failure (HF), pleural effusion results from increased interstitial fluid in the lung due to elevated pulmonary capillary pressure. Rarely, pleural effusions may occur in association with isolated right HF. HF-associated effusions are typically bilateral, but if unilateral, they are more commonly seen on the right side. The fluid typically meets the biochemical characteristics of a transudate, although in 25% of the cases it may fall into the exudative range. Testing for natriuretic peptides, such as NT-proBNP, significantly aids in diagnosing or excluding HF in patients with pleural effusion of unknown origin. The measurement of pleural fluid NT-proBNP is the best way to identify pleural effusions that meet the exudative criteria of Light but are due to HF. However, if natriuretic peptide assays are not available, calculation of the serum to pleural fluid albumin gradient represents a good substitute for making this distinction. Loop diuretics are the mainstay of therapy, although a therapeutic thoracentesis for very large effusions may occasionally be required.

Thoracoscopy with two bronchoscopes in 50 patients with pleural effusion of unknown origin

When performing thoracoscopy in patients with pleural effusion of unknown origin, we used two bronchoscopes simultaneously, one for observation and one for biopsy. A total of 50 patients with pleural effusion of unknown origin were studied. In all of those studies, pleural effusion was exudative, lymphocyte-dominant, had a low level of adenosine deaminase, no malignant cells, and no tuberculosis or other bacteria in pleural effusion smears. Fourteen were out-patients. A catheter was inserted into the pleural space under local anesthesia, and 300 ml to 500 ml of pure oxygen was injected to create a pneumothorax. Two flexible fiberoptic bronchoscopes were used simultaneously, one for observation and one for biopsy. Approximately 1 hour after the examination, the out patients were able to return home. Lesions in the pleural cavity were found in 42 of these 50 patients, and histological diagnosis was possible in 46. This is a simple procedure with no major side effects. The equipment required is familiar to pulmonary physicians, and the diagnostic yield is high.

Reactive oxygen metabolites can be used to differentiate malignant and non-malignant pleural efffusions

OBJECTIVE:Increase in reactive oxygen metabolites (ROM) and free radicals is an important cause of cell injury. In this study, we investigated whether determination of ROM in pleural fluids of patients with malignant and non-malignant pleural effusions can be used as a tumor marker indicating malignant effusions in the differential diagnosis.METHODS:Sixty subjects with exudative pleural effusion and 25 healthy individuals as the control group were included in the study. Of the subjects with pleural effusion, 50% were malignant and 50% were non-malignant. ROM was studied in the pleural fluids and sera of the subjects with pleural effusion and in the sera of those in the control group. The ROM values of smokers and non-smokers were compared in each group. The Student’s t-test and the Mann-Whitney U test were used in order to detect differences between groups for descriptive statistics in terms of pointed features. The statistical significance level was set at 5% in computations, and the computations were made using the SPSS (ver.13) statistical package programRESULTS:It was determined that the difference between the ROM values of subjects with malignant and non-malign pleural effusions and the sera of the control group was significant in the malignant group compared to both groups (P = 0.0001), and the sera ROM values of patients with non-malignant pleural effusion were significant compared to the control group (P = 0.0001), and the ROM values of smokers were significant compared to non-smokers in each of the three groups (P = 0.0001).CONCLUSION:These findings indicate that sera ROM levels are increased considerably in patients with exudative effusions compared to that of the control group. This condition can be instructive in terms of serum ROM value being suggestive of exudative effusion in patients with effusions. Furthermore, the detection of pleural ROM values being significantly higher in subjects with malignant pleural effusions compared to non-malignant subjects suggests that ROM can be used as a tumor marker in the differential diagnosis of pleural effusions of unknown origin.

超高齢男性に発症した原発性滲出液リンパ腫の1例

We report a 90-year-old man who was given a diagnosis of pleural effusion lymphoma (PEL) based on the detailed immunochemical and DNA analyses of the pleural effusion. He was bed-ridden and on enteral nutrition due to severe Alzheimer's disease, and also had diabetes mellitus. He was transferred to our hospital with fever and massive pleural effusion. A cytological examination of the pleural effusion revealed class 5 atypical lymphocytes with a high nucleus/cytoplasm ratio. The origin of the atypical cells could not be determined by flow cytometry of the pleural effusion, which only suggested the existence of inflammatory changes. Considering his general physical status, further investigations were not performed. The respiratory failure progressed, and he died on the 45(th) hospital day. At autopsy, no atypical cells were identified in his organs other than in the right thoracic space. We conducted immunochemical staining after making a cell block from the effusion sample. Most of the atypical cells were CD30 positive, with human herpes virus-8 (HHV-8)-associated protein. A PCR analysis of the immunoglobulin heavy chain gene detected monoclonal rearrangement, thus indicating the atypical cells to be involved in the B-cell lineage. These findings led to a final diagnosis of PEL. PEL is a rare type of lymphoma confined to the body cavities without any prominent tumor mass, and its pathogenesis is related to HHV-8 infection. PEL develops mostly in immunocompromised patients, such as those with AIDS. However, it may also occur in elderly patients as well. We should therefore also consider the possibility of PEL in elderly patients presenting with pleural effusion of unknown origin.

Autofluorescence videothoracoscopy in exudative pleural effusions: preliminary results

Videothoracoscopy has been proven to be a safe tool to establish the diagnosis in >90% of patients with exudative pleural effusions of unknown origin. In the majority of patients with malignant pleural diseases, the endoscopic appearance of pleural lesions during white light thoracoscopy is suggestive of malignancy, but could be misleading in some cases. The aim of the present study was to estimate whether the combination of thoracoscopy with autofluorescence modalities would be useful to further improve the diagnostic accuracy of the conventional method. The present study displays early results of thoracoscopy performed consecutively with a normal light source and with autofluorescence light in 24 patients with exudative pleural effusion during 2003-2004. In all cases of malignant pleuritis (carcinoma or mesothelioma), the colour of the affected area of the pleura changed from white/pink to red (sensitivity 100%). However, in two cases of chronic pleuritis, a colour change from white/pink to orange/red was recorded (specificity 75%). In conclusion, the calculated positive predictive value of colour change for malignant pleuritis during autofluorescence thoracoscopy in this study was 92%. However, the clinical value of autofluorescence thoracoscopy in daily practice remains to be proven.

Plasma B-Type Natriuretic Peptide in Patients With Pleural Effusions: Preliminary Observations

To address the value of plasma B-type natriuretic peptide (BNP) concentrations as a diagnostic tool for determining the cardiac etiology of pleural effusions, and to determine possible differences of plasma BNP concentrations before and after pleurocentesis in patients with congestive heart failure (CHF). Observational study. Tertiary care hospital. Consecutive series of 64 patients with indications for diagnostic pleurocentesis. The final diagnosis of the underlying disease was assessed by clinical criteria. Seven patients were excluded due to pleural effusions of equivocal origin or due to obvious hemothorax secondary to trauma. Pleurocentesis attempting to drain effusions dry. Plasma BNP concentrations were measured directly before pleurocentesis and 24 h after the intervention. During these 24 h, the dosages of patients' medications were held constant. In distinguishing between patients with pleural effusions caused by CHF (n = 31) and patients with pleural effusions attributable to other causes (n = 26), the area under the curve was 0.974 (SE, 0.021; 95% confidence interval, 0.892 to 0.997) for plasma BNP. A BNP cutoff concentration of 2,201 ng/L had a sensitivity of 77% and a specificity of 100% in the diagnosis of CHF. The median plasma BNP concentrations in patients with pleural effusions caused by CHF (n = 31) did not change within 24 h after pleurocentesis compared with the concentrations obtained before the procedure (before pleurocentesis, 3,227 ng/L; 24 h after pleurocentesis, 2,759 ng/L; p = 0.189), despite a median removal of 1,100 mL pleural fluid. Plasma BNP concentrations of patients with pleural effusions of unknown origin may be an aid in the diagnosis of CHF as the underlying cause. If plasma BNP is used as a surrogate marker of global cardiac function, there is no indication of hemodynamic improvement caused by pleurocentesis alone in patients with CHF and pleural effusions.

Medical thoracoscopy.

Thoracoscopy has received increasing attention over the past decade as a result of the considerable advances that have been made in the development of endoscopic instruments. In contrast to the newly established video-assisted thoracoscopic surgery, the classic way to perform thoracoscopy is using only local anesthesia and sedation (medical thoracoscopy) making the procedure less invasive and expensive. The leading diagnostic indication for medical thoracoscopy today is an exudative pleural effusion of unknown origin offering a yield of more than 90% in malignancy or tuberculous pleurisy. In addition, talc poudrage during thoracoscopy is the most effective way to perform pleurodesis. For spontaneous pneumothorax, the second most important indication, medical thoracoscopy allows staging as well as therapeutic measures such as coagulation of blebs or talc poudrage. Other indications such as biopsy for diffuse lung disease or peripheral nodules are now reserved for video-assisted thoracoscopic surgery.