Transudative malignant pleural effusions
David McCrackenRachel MercerMata TsikrikaRebecca VaratharajahAndrew ThayanandanQiang LüGillian ShephardEihab O. BedawiRachelle AsciakJohn WrightsonNajib M. Rahman
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Abstract:
Introduction: The incidence of transudative malignant pleural effusion is unclear but is suggested to be between 1- 17.4%.[1] Management and prognostication is also poorly defined. We present results from the largest cohort to date. Method: Complete follow up data was retrospectively collected and analysed for all patients undergoing pleural fluid sampling at Oxford University Hospitals NHS Foundation Trust between January 2015 and December 2017 inclusive. This included samples obtained from procedures performed by the pleural, respiratory and radiology teams. Results: 981 patients were included of which 306 had malignant pleural effusion. 10 of these were transudative (3.3%). 5 patients (50%) were male with an average age of 69.2 years. 9 of 10 (90%) had either a known current or previous diagnosis of malignancy. 5/10 (50%) demonstrated positive pleural fluid cytology, 1/10 (10%) had malignant pleural disease confirmed on histology from a subsequent pleural biopsy and 4/10 (40%) received a clinical diagnosis of malignant pleural effusion. Only 2 patients underwent talc pleurodesis of which neither was successful. 1 was managed with an indwelling pleural catheter and the rest with either symptomatic drainage or palliative care. Median survival was 34 days with an interquartile range of 11-76.5. Conclusions: A small but significant number of malignant pleural effusions demonstrate transudative features, suggesting that MPE should not be excluded solely using biochemistry. Talc pleurodesis may have a lower success rate in transudative effusions, however long term management considerations may be less relevant in this cohort as patients appear to have a much lower median survival. 1. Ferreiro, L. et al. J thorac dis, 2017. 9(1):106-116Keywords:
Pleurodesis
Pleural disease
Interquartile range
Malignant pleural effusion is a significant cause of morbidity and a poor prognostic indicator. Traditional treatments have variable success and significant drawbacks, including a length of stay in the hospital. Alternatively, a tunneled pleural catheter permits long-term drainage as an outpatient, cost-effectively controlling the effusion and related symptoms in over 80 to 90% of patients. Other advantages are the ability to treat trapped lungs and large locules. Spontaneous pleurodesis may occur in over 40% of patients, and the catheter can be used to administer sclerosant or antineoplastic agents. Complications tend to be minor and easily managed. A tunneled pleural catheter should be considered for all patients with MPE having a reasonable expectancy of being an outpatient.
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Pleural effusion is a frequently encountered medical problem and malignant pleural effusion complicates the course of various types of cancer.1 Since the finding of pleural involvement has significant prognostic implications, determining the cause of pleural effusion is essential.1 Thoracoscopy and pleural biopsies are recommended when the cause of pleural effusion cannot be defined by pleural fluid analysis.2–4 Thoracoscopy is often used with both a diagnostic and a therapeutic aim, since it can be combined with talc poudrage in appropriate cases.5 Given the diagnostic and therapeutic potentials, it would be beneficial if physicians could accurately predict malignancy during diagnostic thoracoscopy. Immediate feedback with a diagnosis of malignancy could prevent the need of a second thoracoscopy for pleurodesis. Similarly, predicting tuberculosis with high degree of accuracy would be beneficial by starting treatment early and not subjecting the patient to additional and potentially harmful interventions. We know that visual differentiation of malignant from benign pleural disease is poor even among the most experienced thoracoscopists.6 In addition there is scarcity of data on diagnostic accuracy of frozen section evaluation as well as rapid onsite evaluation (ROSE) of imprint cytology (a.k.a., touch preparations or touch preps) during thoracoscopy. The degree of accuracy of imprint cytology was recently reported by Gupta et al.7 In this retrospective study, the authors reviewed 66 cases and found a diagnostic yield of 89% for thoracoscopic pleural biopsy imprint cytology. In cases of malignancy, the sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and negative likelihood ratio (LR) of imprint cytology were 92%, 100%, 100%, 76%, and 0.08, respectively.7 In cases of tubercular pleural effusions, the sensitivity, specificity, PPV, NPV, and negative LR of imprint cytology were 75%, 100%, 100%, 95%, and 0.25, respectively.7 The finding of granulomas was considered as true-positive for cases of tuberculosis. The authors reported 0 false-positives and no indeterminate cases.7 In the authors' practice environment, the imprint cytology results were available ∼2.5 days earlier than the biopsy results. The demonstrated reliability of their cytology results would permit initiating an earlier treatment, triage, and discharge from hospital. The study by Gupta and colleagues had a few limitations, including a retrospective design and a small sample size of 66 patients. In addition, the study design may have introduced a selection bias by only including those patients with significant thoracoscopic findings.7 Selection bias is a fundamental problem of most observational studies as there is no set a priori parameter for the allocation of the patients in the imprint cytology group. Hence, it is possible that the touch prep was used only in the most abnormal or difficult cases in which the physician would want to obtain the most information from the procedure. Obtaining touch preps on all consecutive subjects undergoing a thoracoscopy procedure with a fuller description of the subjects and the method of their recruitment would have minimized the effect of selection bias. In addition, measures of diagnostic accuracy such as sensitivity and specificity are very sensitive to the design of the study as well as to the characteristics of the population in which the test accuracy is evaluated. Diagnostic studies with methodological shortcomings risk overestimating the accuracy of a diagnostic test and should be interpreted with caution. Touch preps are typically used in the setting of ROSE to guide intraprocedural decisions; however, the data presented in this study would not directly correlate with ROSE results for 2 main reasons. First, the cytopathologists in this study had more stains available (May-Grunwald-Giemsa, Pap, and hematoxylin and eosin) than is practical in an immediate assessment environment. Second, the cytopathologists had considerably more time to study the slides (average time to final report of 3.2 d). Yet, the data do underscore the diagnostic power of this simple test and potential for use during thoracoscopy. There are few studies to evaluate ROSE of touch preps during thoracoscopy. The study of Porfyrides reported a sensitivity of 79%; specificity, 94%; diagnostic accuracy, 88%; PPV, 90%; and NPV, 87%.8 In addition, we reported from our institution LRs with only the finding of "no malignancy" on ROSE of touch preps being statistically significant, with an LR of 0.11 (95% confidence interval: 0.01-0.93). The area under the receiver operating characteristic curve was poor at 0.57 (95% confidence interval: 0.40-0.75).9 We chose LR as opposed to sensitivity and specificity, as LRs are a better to describe the utility of a particular test result, specifically when there are >2 possible test results.9 Gupta and colleagues have shown that imprint cytology provided earlier etiological diagnoses than biopsy histology in their practice, which could result in decreased hospital stay duration and health care expenditure and permit earlier clinical triage and treatment. They hypothesize that when combined with ROSE, imprint cytology has the potential to decrease the number of acquired biopsies and procedure-associated complications and shorten the duration of procedure. We do agree that much information can be obtained from touch preparations. In thoracoscopic procedures they are most useful in assessing the adequacy of biopsied tissue, but definitive diagnosis during ROSE can be limited by time constraints and the high degree of atypia common in reactive mesothelial proliferations. Decision making during thoracoscopy begins before the procedure with a thorough understanding of the clinical presentation and prethoracoscopy imaging and then with an estimation of the pretest probabilities of the various diagnostic possibilities. The beneficial and harmful consequences of various intraprocedural interventions or treatment strategies must be weighed. While touch preps may provide useful diagnostic information in a subset of cases in the appropriate clinical settings, we believe that the data on the general applicability of ROSE of touch preps to firmly guide intraprocedural decision making are not quite there yet. Hopefully with further research and prospective data design, the real benefit of adding ROSE of touch preps to thoracoscopy procedures will be elucidated.
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Malignancy is the leading cause of exudative pleural effusion in patients over 60. Several techniques for palliative treatment of malignant pleural effusions (MPE) are recommended; in particular, sclerosing agents have been instilled into the pleural cavity. In up to 30%, recurrence of MPE cannot be prevented. In recent years excellent results (recurrence rate less than 10%) have been reported using the technique of thoracoscopic talkage. After a review of the most frequent techniques of pleurodesis, a treatment strategy, mentioning the indications for the thoracoscopic procedure, is presented stressing the following guidelines: after complete thoracocentesis the patient's respiratory symptoms should decrease significantly and the compressed lung must be expanded clinically and radiologically after drainage. For patients fulfilling these conditions thoracoscopic pleurodesis is an effective initial treatment. It seems to be a safe procedure with minor side effects even for patients in a reduced general condition.
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Pleural effusion from metastatic malignancy can cause major impairment of respiratory function and eventual death. Although cure is not possible, successful palliative treatment allows months to years of productive life, obviating the need for continuous hospitalization and repeated thoracenteses. Successful palliative treatment requires obliteration of the pleural space. Literature survey indicates that a wide variety of medical agents and surgical methods have been used with variable success. Medical methods include instillation of antineoplastic agents, antimicrobial agents, or colloidal radioisotopes into the pleural space; quinacrine and tetracycline are moderately to highly effective agents, but the toxicity of the former is substantial. Bedside talc poudrage with thoracostomy-tube drainage is a safe and highly effective alternative. Pleurectomy is the definitive method of preventing reaccumulation of pleural fluid that results from metastatic malignancy, even when other methods have failed, but the high morbidity and mortality of the procedures mandate careful patient selection.
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Recurrent malignant pleural effusion (MPE) is a common concomitant phenomenon of malignant disease, which can worsen the patient's quality of life and lead to significant morbidity. Tunneled indwelling pleural catheters (TIPC) offer new modalities in patients with recurrent MPE and impaired dilatability of the lung. We report on our experience with 100 consecutive patients suffering from recurrent benign (n = 12) and malignant pleural effusion (n = 88) who were treated with TIPC. The catheter was placed during a VATS procedure or under local anesthesia in an open technique. The median residence time of the TIPC was 70 days; spontaneous pleurodesis was achieved in 29 patients. The rate of complications was low: pleura empyema (n = 4), accidental dislodgement (n = 2), malfunction of the drainage (n = 3). In conclusion, TIPC is a useful method for the palliative treatment of patients with recurrent malignant or nonmalignant pleural effusions and 3 groups of patients seem to benefit most: a) patients with the intraoperative finding of a trapped lung in diagnostic VATS procedure; b) patients after a history of repeated pleuracenteses or previously failed attempts at pleurodesis; c) patients in a reduced condition with a limited lifespan due to underlying disease.
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Background:
Malignant pleural effusion (MPE) is a common clinical problem with described investigation pathways. While thoracic ultrasound (TUS) has been shown to be accurate in pleural fluid detection, its use in the diagnosis of malignant pleural disease has not been assessed. A study was undertaken to assess the diagnostic accuracy of TUS in differentiating malignant and benign pleural disease.Methods:
52 consecutive patients with suspected MPE underwent TUS and contrast-enhanced CT (CECT). TUS was used to assess pleural surfaces using previously published CT imaging criteria for malignancy, diaphragmatic thickness/nodularity, effusion size/nature and presence of hepatic metastasis (in right-sided effusions). A TUS diagnosis of malignant or benign disease was made blind to clinical data/other investigations by a second blinded operator using anonymised TUS video clips. The TUS diagnosis was compared with the definitive clinical diagnosis and in addition to the diagnosis found at CECT.Results:
A definitive malignant diagnosis was based on histocytology (30/33; 91%) and clinical/CT follow-up (3/33; 9%). Benign diagnoses were based on negative histocytology and follow-up over 12 months in 19/19 patients. TUS correctly diagnosed malignancy in 26/33 patients (sensitivity 73%, specificity 100%, positive predictive value 100%, negative predictive value 79%) and benign disease in 19/19. Pleural thickening >1 cm, pleural nodularity and diaphragmatic thickening >7 mm were highly suggestive of malignant disease.Conclusion:
TUS is useful in differentiating malignant from benign pleural disease in patients presenting with suspected MPE and may become an important adjunct in the diagnostic pathway.Pleural disease
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Objective: To determine the presence or not of idiopathic pleuritis in patients that underwent medical thoracoscopy(MT) Materials and methods: Retrospective study of 750 patients (1998-2011) that underwent MT under conscious and local sedation. Assessment of clinicopathological status/results and clinical follow up in the thoracic outpatients clinic. Results: Thirty two patients were excluded from the group of patients with undiagnosed pleural effusion (histology report:systemic disease or parapneumonic effusion).152/770 patients(20.2%)were classified as idiopathic pleuritis (sinister and any other underlying pathology was excluded) and underwent long term surveillance. Mean surveillance was 4.1 years(2months–9years). During that time 2/152 was diagnosed with lung cancer. 3/152 presented pleural effusion recurrence without any signs of malignancy/systemic disease and underwent talc pleurodesis. Conclusions: Undiagnosed pleural effusions constitute a large group among the pleural effusion patients. This group is associated with favourable patient outcome and encouraging prognosis especially when the diagnosis is set by MT under conscious sedation.
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