Diagnostic method for malignant pleural effusion distinguishing malignant mesothelioma from lung cancer using pleural carcinoembryonic antigen and hyaluronic acid levels

Malignant mesothelioma (MM) is difficult to diagnose because of the lack of parenchymal opacities, often revealing minimal or absent pleural thickening. Furthermore, pleural effusion has diverse differential diagnoses, including malignancies, infections, as well as collagen vascular and other benign diseases. In general practice, lung cancer (LC) is the most common malignancy causing pleural effusion; therefore, a simple method using pleural diagnostic markers to differentiate between LC and mesothelioma is crucial.We retrospectively reviewed the data of 530 adult patients diagnosed with pleural effusion between January 2010 and December 2020 in an outpatient or inpatient setting. Patients with pathologically diagnosed MM or LC with cytologically positive (class IV or V) pleural effusion were analyzed, and the characteristics of these 2 diseases were compared.During the study period, 27 patients diagnosed with MM and 100 patients diagnosed with LC were enrolled. Receiver operating characteristic curve analysis demonstrated that pleural carcinoembryonic antigen (CEA) and hyaluronic acid (HA) could discriminate MM from LC with an area under the curve of 0.925 (95% confidence interval [CI]: 0.879–0.972, P < .001) and 0.815 (95% CI: 0.686–0.943, P < .001), respectively. To diagnose MM, the accuracy of pleural HA >30,000 ng/mL revealed a sensitivity of 75.0%, specificity of 72.6%, and odds ratio of 7.94 (95% CI: 2.5–25.2, P = .001); pleural CEA <6.0 ng/mL revealed a sensitivity of 95.2%, specificity of 84.9%, smaller negative likelihood ratio of 0.06, and odds ratio of 112.5% (95% CI: 14.4–878.1, P < .001). Multiple logistic regression analysis revealed that these 2 parameters could discriminate MM from LC, with a hazard ratio of 23.6 (95% CI: 2.437–228.1, P = .006) and 252.3 (95% Cl: 16.4–3888.1, P < .001), respectively, and their combination had a high specificity of 98.3%.Pleural CEA (≥6.0 ng/mL) can rule out MM with a high degree of certainty, and the positive results for combination of pleural CEA <6.0 ng/mL and HA >30,000 ng/mL can confirm MM with high specificity, prior to cytological or pathological examinations.     

Clinicopathological analysis of lung cancer resembling malignant pleural mesothelioma

OBJECTIVE: The aim of this study was to evaluate the clinicopathological features of lung cancer resembling malignant pleural mesothelioma. METHODOLOGY: The seven patients studied had tumours showing an extensive pleural growth pattern, and were chosen from 1516 lung cancer patients diagnosed at two affiliated hospitals over a 17-year period. RESULTS: Histologically, five of these lung cancers were adenocarcinomas, one was a small cell carcinoma, and one a large cell carcinoma. Tumour markers such as carcinoembryonic antigen (CEA) were elevated in six patients at admission. However, a clinical diagnosis was difficult and these cancers could only be distinguished from malignant pleural mesothelioma by thoracentesis in two cases, pleural biopsy in two, thoracotomy in two, and in case 7 at autopsy. Treatment consisted of chemotherapy or radiation therapy in four patients, but with little clinical effect. The mean survival time was 6.7 months, which is much less than for true malignant pleural mesothelioma. CONCLUSIONS: Lung cancer resembling malignant pleural mesothelioma is most frequently observed in patients with adenocarcinoma, which is suspected to occur peripherally. To distinguish pseudomesotheliomatous carcinoma from malignant pleural mesothelioma in patients with diffuse pleural thickening and effusion, requires adequate tissue sampling by thoracotomy or video-assisted thoracoscopic surgery and a panel of immunohistochemical stains.     

Relation of body fluid status to B-type natriuretic peptide levels in patients with chronic heart failure during long-term follow-up

BACKGROUND: Little is known about the relationship of body fluid status with the levels and fluctuations of B-type natriuretic peptide (BNP) over the long-term. Hypothesis: If BNP is to become useful for monitoring of patients with chronic heart failure (HF), the levels should reliably reflect both decompensation and improvement in the patient's condition. METHODS: Forty-six patients with chronic HF who were stable at study entry but had previous decompensation were recruited and followed up between June 2003 and September 2005. At each visit, they were examined for BNP level and HF-related signs of body fluid retention based on physical evaluation and pleural ultrasonography. RESULTS: During the study period, 26 patients developed decompensation and 20 maintained a stable clinical course. In the 26 decompensated patients, BNP levels fluctuated widely (110 +/- 73.7 pg/ml; range 25-290 pg/ml) even during stable periods. In all but three patients in this group, the maximum BNP level during decompensation was higher than that reached during stable periods. The BNP levels also fluctuated widely (180 +/- 123 pg/ml; range 16-489 pg/ml) in the 20 stable patients with HF. In all but one patient in this group, the BNP level was lower than the maximum BNP level obtained during the previous decompensation. CONCLUSIONS: In patients with chronic HF with previous decompensation, there was a strong link between the appearance of clinical HF sign(s) of fluid retention and an increased BNP level despite wide intraindividual fluctuations in BNP over time. Thus, BNP levels reliably reflect both decompensation and improvement.     

Clinical usefulness of B-type natriuretic peptide in the diagnosis of pleural effusions due to heart failure

Background and objective: Light's criteria are frequently used to evaluate the exudative or transudative nature of pleural effusions. However, misclassification resulting from the use of Light's criteria has been reported, especially in the setting of diuretic use in patients with heart failure (HF). The objective of this study was to evaluate the utility of B‐type natriuretic peptide (BNP) measurements as a diagnostic tool for determining the cardiac aetiology of pleural effusions. Methods: Patients with pleural effusions attributable to HF (n = 34), hepatic hydrothorax (n = 10), pleural effusions due to cancer (n = 21) and pleural effusions due to tuberculosis (n = 12) were studied. Diagnostic thoracentesis was performed for all 77 patients. Receiver operating characteristic (ROC) curves were constructed to determine the diagnostic accuracy of plasma BNP and pleural fluid BNP for the prediction of HF. Results: The areas under the ROC curves were 0.987 (95% CI 0.93–0.998) for plasma BNP and 0.949 (95% CI 0.874–0.986) for pleural fluid BNP, for distinguishing between patients with pleural effusions caused by HF (n = 34) and those with pleural effusions attributable to other causes (n = 43). The cut‐off concentrations with the highest diagnostic accuracy for the diagnosis of HF as the cause of pleural effusion were 132 pg/mL for plasma BNP (sensitivity 97.1%, specificity 97.4%) and 127 pg/mL for pleural fluid BNP (sensitivity 97.1%, specificity 87.8%). Conclusions: In patients with pleural effusions of suspected cardiac origin, measurements of BNP in plasma and pleural fluid may be useful for the diagnosis of HF as the underlying cause.     

Malignant peritoneal mesothelioma a clinical and laparoscopic study of ten cases

Summary A retrospective study of 10 cases of malignant peritoneal mesothelioma from two centers is reported. All cases were initially diagnosed between 1967 and 1986 utilizing laparoscopy and the histologic interpretation of laparoscopic biopsy samples. Subsequently, the original diagnosis was confirmed by two independent pathologists employing both histological and histochemical techniques. In five cases immunohistochemical studies were also performed. The clinical findings and course of the disease were similar to other reported series. Laparoscopic findings of mesothelioma were indistinguishible from metastatic peritoneal neoplasms. However, the presence of homogeneous spreading of nodules, plaques, or fleshy masses on both parietal and visceral peritoneum; the absence of direct or indirect signs of other abdominal neoplasms; and the absence of hepatic metastases or the possible presence of nodules or plaques on Glisson's capsule without any parenchymal involvement, when observed, allowed the laparoscopist to suspect the disease in four of 10 cases. Laparoscopy may be useful in detecting mesothelioma. The diagnosis is mainly morphological, but even morphology has its inherent limitations. Further studies are necessary to improve the diagnostic accuracy of this tumor.A part of this study was presented during the 12th International Congress of Gastroenterology and the 5th International Congress of Gastrointestinal Endoscopy in Lisbon, Portugal, September 16–22, 1984.     

Biological variation of the natriuretic peptides and their role in monitoring patients with heart failure

BACKGROUND: B-type natriuretic peptide (BNP) and the inactive metabolite NT-proBNP are proven tests for diagnosis and staging of severity for patients with heart failure. However, the utility of these biomarkers for monitoring the success of drug therapy remains to be determined. Results of longitudinal studies on serial blood testing must be linked to overall patient morbidity and mortality outcomes. We previously determined the 8-week biological variability (BV) of BNP and NT-proBNP assays in healthy subjects and the 1-day BV for BNP alone in patients with compensated and stable heart failure. From these studies, the percent statistical change in serial samples of approximately 100% difference was estimated (95% confidence). METHODS: We applied the biological variability concepts to the serial results of BNP and NT-proBNP collected from patients with heart failure and compared the performance of these two markers. RESULTS: While there are minor differences in the results between the assays from one time period to another, the overall interpretation of results are essentially identical. Moreover, the majority of individual serial time points are not significantly different from the previous value. CONCLUSION: Frequent testing (e.g. daily) for BNP and NT-proBNP to monitor therapy for patients with CHF is not indicated, as overall changes require several days to become evident.     

Pleural effusions and pneumothorax: Beyond simple plumbing

Pleural diseases affect millions of people worldwide. Pleural infection, malignant pleural diseases and pneumothorax are common clinical challenges. A large number of recent clinical trials have provided an evidence‐based platform to evaluate conventional and novel methods to drain pleural effusions/air which reduce morbidity and unnecessary interventions. These successes have generated significant enthusiasm and raised the profile of pleural medicine as a new subspecialty. The ultimate goal of pleural research is to prevent/stop development of pleural effusions/pneumothorax. Current research studies mainly focus on the technical aspects of pleural drainage. Significant knowledge gaps exist in many aspects such as understanding of the pathobiology of the underlying pleural diseases, pharmacokinetics of pleural drug delivery, etc. Answers to these important questions are needed to move the field forward. This article collates opinions of leading experts in the field in highlighting major knowledge gaps in common pleural diseases to provoke thinking beyond pleural drainage. Recognizing the key barriers will help prioritize future research in the quest to ultimately cure (rather than just drain) these pleural conditions.     

Interventional therapies for malignant pleural effusions: The present and the future

The approach to management of malignant pleural effusions (MPE) has changed over the past few decades. The key goals of MPE management are to relieve patient symptoms using the least invasive means and in the most cost‐effective manner. There is now a realization that patient‐reported outcome measures should be the primary goal of MPE treatment, and this now is the focus in most clinical trials. Efforts to minimize patient morbidity are complemented by development of less invasive treatments that have mostly replaced the more aggressive surgical approaches of the past. Therapeutic thoracentesis is simple, effective and generally safe, although its benefits may only be temporary. Pleurodesis is the conventional and for a long time the only definitive therapy available. However, the efficacy and safety of talc pleurodesis has been challenged. Indwelling pleural catheter (IPC) drainage is increasingly accepted worldwide and represents a new concept to improve symptoms without necessarily generating pleural symphysis. Recent studies support the effectiveness of IPC treatment and provide reassurance regarding its safety. An unprecedented number of clinical trials are now underway to improve various aspects of MPE care. However, choosing an optimal intervention for MPE in an individual patient remains a challenge due to our limited understanding of the underlying pathophysiology of breathlessness in MPE and a lack of predictors of survival and pleurodesis outcome. This review provides an overview of common pleural interventional procedures used for MPE management, controversies and limitations of current practice, and areas of research most needed to improve practice in future.     

肺癌合并恶性胸腔积液化疗前后CEA、NSE、SCC-Ag的表达及意义

目的探讨肿瘤标志物CEA、NSE和SCC-Ag在肺癌合并恶性胸腔积液的诊断和评估近期疗效的价值。方法用电化学发光法分别检测肺癌合并恶性胸腔积液患者(实验组)和良性胸腔积液患者(对照组)血清及胸水中CEA、NSE和SCC-Ag水平,及实验组化疗后血清上述肿瘤标志物水平。结果实验组血及胸水中CEA、NSE、SCC-Ag水平均高于对照组(P0.05);化疗有效组血中CEA、NSE、SCC-Ag水平均低于化疗前(P0.05);化疗失败组血中CEA水平明显高于化疗前(P0.05),NSE、SCC-Ag水平无明显变化(P0.05)。结论 CEA、NSE、SCC-Ag对肺癌合并恶性胸腔积液的诊断有指导意义,CEA能判断肺癌合并恶性胸腔积液患者化疗的近期疗效。     

B-type natriuretic peptide measurement in heart failure

Serum testing for the hormone B-type natriuretic peptide (BNP) may have clinical utility in congestive heart failure (CHF). This hormone is secreted predominantly by the left ventricular myocardium in patients with CHF. Measurement of serum BNP may improve diagnosis of CHF and may also help guide therapy in patients with CHF. The literature regarding the clinical utility of BNP measurement in CHF is reviewed.     

Determinants and clinical significance of natriuretic peptides and hypertrophic cardiomyopathy.

AIMS: Atrial and brain natriuretic peptide levels closely reflect impaired left ventricular function in patients with heart failure. In the present study we assessed the determinants and the clinical significance of atrial and brain natriuretic peptide plasma levels in hypertrophic cardiomyopathy. METHODS AND RESULTS: In 44 patients with hypertrophic cardiomyopathy (40+/-15 years) we evaluated: (a) atrial and brain natriuretic peptide plasma levels; (b) left ventricular hypertrophy; (c) left ventricular ejection fraction; (d) transmitral and pulmonary venous flow velocity patterns, and left atrial fractional shortening; (e) left ventricular outflow tract gradient; (f) maximal oxygen consumption. Left ventricular hypertrophy influenced only brain natriuretic peptide levels (r=0.32;P<0.05). Atrial and brain natriuretic peptide plasma levels did not correlate with left ventricular ejection fraction, but correlated with left ventricular outflow tract gradient (r=0.35;P<0.05; and r=0.40, P=0.022, respectively) and left atrial fractional shortening (r=-0.57;P<0.001, and r=-0.35;P<0.05, respectively). Atrial but not brain natriuretic peptide plasma levels were inversely related to maximal oxygen consumption (r=-0.35;P<0.05). By stepwise multiple regression analysis, left atrial fractional shortening and left ventricular outflow tract gradient were the only predictors of atrial and brain natriuretic peptide plasma levels, respectively. CONCLUSIONS: In hypertrophic cardiomyopathy, atrial natriuretic peptide plasma levels are mainly determined by diastolic function: this explains the relationship with exercise tolerance. In contrast, brain natriuretic peptide plasma levels are mainly determined by left ventricular outflow tract gradient.     

胸膜粘连术对恶性浆膜腔积液的疗效观察

目的观察顺铂联合草分枝杆菌F.U.36治疗恶性胸水/心包积液的疗效和安全性。方法采用中心静脉导管置入法,收集我院呼吸内科和肿瘤内科收治的30例肺癌伴胸水/心包积液的病例。结果 30例患者中,完全缓解23例,部分缓解2例,无效5例,总有效率达83.3%。结论胸腔内置管并注入冻干顺铂、草分枝杆菌F.U.36治疗肺癌引起的恶性积液疗效显著,副反应少,操作简单,值得临床应用。     

The diagnostic accuracy of plasma BNP and NTproBNP in patients referred from primary care with suspected heart failure: results of the UK natriuretic peptide study

OBJECTIVES: To determine the diagnostic accuracy of the measurement of plasma B-type natriuretic peptide (BNP) and N-terminal pro-BNP (NTproBNP) in patients referred by their general practitioners (GPs) with symptoms suggestive of heart failure. Additionally, to compare the diagnostic accuracy of the resting 12-lead electrocardiogram (ECG) with that of the peptides. DESIGN: A diagnostic accuracy study. SETTING: Rapid-access heart failure clinics in five hospitals. PARTICIPANTS: 306 patients referred by their GPs with suspected heart failure. MAIN OUTCOME MEASURES: Sensitivity, specificity, positive and negative predictive values (PPV and NPV) and positive and negative likelihood ratios for BNP, NTproBNP and the ECG for the diagnosis of heart failure. Area under the receiver operating characteristics (ROC) curves for the two natriuretic peptides. RESULTS: The diagnosis of heart failure was confirmed in 104 (34%) patients. The area under the ROC curve was 0.84 [95% CI 0.79-0.89] for BNP and 0.85 [0.81-0.90] for NTproBNP. At the manufacturers' recommended decision cut-points, NTproBNP provided a higher NPV (0.97) than BNP (0.87), but at lower PPV (0.44 versus 0.59). An abnormal ECG did not add any further predictive value to that of NTproBNP. CONCLUSIONS: We have confirmed the value of the measurement of plasma BNP or NTproBNP as a 'rule-out' test for heart failure in patients currently referred by GPs to rapid access diagnostic clinics. A simple classification of the 12-lead ECG into 'normal' or 'abnormal' adds little value to ruling out heart failure in these circumstances. Further work is necessary to establish the best decision cut-points for use in clinical practice.