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Interact CardioVasc Thorac Surg 2006;5:307-310. doi:10.1510/icvts.2005.118018 © 2006 European Association of Cardio-Thoracic Surgery
Life expectancy of patients with malignant pleural effusion treated with video-assisted thoracoscopic talc pleurodesis
a Department of Cardiovascular and Thoracic Surgery, Tartu University Clinics, Puusepa 8, 51014 Tartu, Estonia Received 8 August 2005; received in revised form 27 January 2006; accepted 22 February 2006
*Corresponding author. Tel.: +372 53 318 055; fax: +372 7 318 299.
The aim of the current study was to analyse postoperative complications and survival after video-assisted thoracoscopic (VATS) talc pleurodesis for malignant pleural effusion. All patients with morphologically proven malignant pleural effusion who underwent VATS talc pleurodesis from November 1995 to November 2002 were included in retrospective analysis. VATS was performed in general anaesthesia and 5 g of asbestos-free talc was insufflated into the pleural cavity. Postoperative pleural drainage was used until fluid output was less than 100 ml/24 h. Ninety-eight patients (28 male and 70 female) with mean age 59.6 (range 18–82) years were included. Thirteen patients had a bilateral pleural effusion. The most common primary cancer sites were lung (30 cases), breast (25) and ovarium (11). Average duration of the operation was 46 (range 10–120) min. Median duration of postoperative drainage was 3 (range 1–20) days and postoperative hospitalisation 7 (range 3–70) days. Twenty-eight patients had postoperative complications (fever in 17 cases). In seven cases pleurodesis was ineffective. Median survival was 8.4 months. Six-, 12- and 24-month survival was 58% (95% CI [0.47–0.67]), 39% [0.29–0.49] and 20% [0.12–0.29], respectively. Survival data after VATS talc pleurodesis advocate use of this invasive treatment method despite the advanced stage of cancer.
Key Words: Malignant pleural effusion; Pleurodesis; Talc; VATS
Patients with pleural metastasis often develop a malignant pleural effusion requiring serial thoracentesis, chest tube drainage, pleuroperitoneal shunting or pleurodesis. The aim of these treatment methods is to improve patients' quality of life by reducing symptoms, mainly dyspnoe, caused by effusion. Effective pleurodesis eliminates the need for multiple hospital visits for removal of pleural fluid by thoracentesis. According to previous reports, thoracoscopic insufflation of talc gives an excellent long-term result in up to 92.7% of patients with malignant pleural effusions [1]. One may assume short survival in patients with advanced cancer, but the majority of studies address only early results of talc pleurodesis, whereas long-term survival is not reported. Moreover, early cases of mortality are usually excluded from analysis and the remaining patients are followed up for a few months only. Due to advanced cancer in these patients, full follow-up is problematic and therefore overall survival of patients after talc pleurodesis for malignant pleural effusion is not well documented. Talc pleurodesis is usually performed in general anaesthesia and requires postoperative drainage and hospitalisation. This kind of invasive treatment may by itself cause some morbidity and mortality. Due to well-documented results of talc pleurodesis, we did not analyse the long-term effect of pleurodesis among our patients, but aimed a study to analyse in-hospital morbidity, mortality and survival of patients who underwent video-assisted thoracoscopic (VATS) talc pleurodesis for malignant pleural effusion.
All patients who underwent VATS talc pleurodesis for treatment of malignant pleural effusion since the introduction of VATS in Tartu University Clinics from November 1995 to November 2002 were included in this retrospective study. VATS talc pleurodesis was the preferred pleurodesis method in our institution and was used in all cases when a patient had a recurrent pleural effusion causing respiratory symptoms (mainly dyspnea) and general status of the patient allowed operation in general anaesthesia. Pre-operative pleural drainage was not routinely used for evaluation of lung re-expansion capacity. In all cases, VATS talc pleurodesis was performed in general anaesthesia with single-lung ventilation. The patient was put in lateral decubitus position. In most cases, two ports of 5 or 10 mm diameter were used. Pleural fluid was evacuated and adhesiolysis was performed when needed to achieve better lung re-expansion. In the majority of cases, except when diagnosis had been established preoperatively, pleural biopsy was taken to confirm the morphological diagnosis. Under direct thoracoscopic vision, 5 g of asbestos-free talc powder was insufflated into the pleural cavity with a manual insufflator to achieve even distribution of talc. At the end of the operation one or two pleural drains were left in place. Chest tubes were connected to suction –20 cm H2O. Discharged pleural fluid volume was recorded on a daily basis and chest tubes removed when fluid output was less than 100 ml/24 h. In the case of prolonged post-operative pleural fluid production, we repeated pleurodesis with talc slurry. Suspension of 5 g of talc in 100 ml of 0.9% NaCl was administered intrapleurally via a chest tube, which remained clamped for 3 h. The tube was removed according to fluid output. A day after chest tube removal a chest radiograph was taken. Patients were discharged in the case of only minimal or no residual pleural effusion and general status allowing out-patient care. Survival data were obtained from the Population Registry. Kaplan–Meier estimates for assessing the survival curves were produced. Log-rank test was applied to test morphology and age effect on survival curve.
During the study period, 101 VATS talc pleurodesis was performed for 98 patients (28 male and 70 female), with mean age 59.6 (range 18–82) years. Thirteen (13.3%) patients had a bilateral pleural effusion. In 10 cases, simultaneous bilateral pleurodesis was performed and it was referred to as one operation in further analysis. In three cases sequential operations were performed after 4, 8 and 12 months. In addition to the 13 patients with bilateral effusions, 53 patients had right-side and 32 left-side effusions. The average duration of the operation was 46 (range 10–120) min. Parietal pleural biopsies were taken in 75 cases. The most common primary cancer sites were lung (30 cases), breast (25 cases), and ovaries (11 cases). Among women, breast cancer, and among men, lung cancer, were the most common cause of pleural metastases. In 8 cases, adenocarcinoma with unknown origin and in 7 cases malignant pleural mesothelioma had caused the pleural effusion. Other primary cancers were represented less frequently (Table 1).
Median duration of postoperative pleural drainage was 3 (range 1–20) days. Median duration of postoperative hospitalisation was 7 (range 3–70) days, which decreased significantly over the years. Median hospitalisation period was 9 days in the first and 5 days during the second half of the study (P=0.0004). Six patients with advanced malignancy died postoperatively in hospital. In five cases distant metastases in other locations (in addition to pleura) were present. In one patient far advanced lymphoma, covering visceral and parietal pleura and causing massive pleural effusions was the cause of death. After 101 VATS operations 28 patients experienced a total of 33 post-operative complications. The most common complication was fever – in 17 cases. Three patients developed postoperative respiratory problems, one of them ARDS. Other complications are listed in Table 2. In four cases pleurodesis was considered ineffective, due to residual cavity, and in three other cases due to permanent fluid discharge from the chest tube. For these patients (two with metastatic breast cancer and one with mesothelioma), talc slurry was administered through chest tube in one case after 7 days and in two cases 8 days following the operation with an excellent final result in all patients.
Survival data were available for all patients except one. At the time of analysis 16 patients were still alive. Median postoperative survival was 8.4 months (Fig. 1). Six-month survival was 58% (95% CI 0.47–0.67), 12-month survival 39% (0.29–0.49), 18-month survival 25% (0.17–0.35) and 24-month survival 20% (0.12–0.29).
No statistical differences in survival were observed when comparing patients with different age (P=0.46) or morphology (Fig. 2). Median survival of patients with metastatic lung cancer was 9.1 months, with breast cancer 7.7 months, with ovarian cancer 3.3 months and other cancers combined 10 months (P=0.7).
Nearly all cancers can cause distant pleural metastases, which, during the course of disease, may result in development of a malignant pleural effusion. Similarly to several previous studies, we observed primary lung cancer to be the most common cause of malignant pleural effusion [1,2]. The second cause was breast cancer, which is the most common cancer among women in Estonia. Surprisingly, the second most common cancer among women causing pleural metastases was lung cancer, although in general lung cancer ranked 7th–8th among cancers in women during these years in Estonia. The presence of malignant pleural effusion eliminates the possibility of radical cancer treatment, but palliative care plays an important role for these patients. Chemical pleurodesis is one of the options to avoid development of recurrent pleural effusions and thus palliate symptoms. Talc seems to be the most widely used agent [3], either in the form of slurry or powder, insufflated into pleural cavity during thoracoscopy or VATS. VATS enables even distribution of talc over the pleural cavity under direct vision, which should improve the quality of pleurodesis. Another advantage is the possibility to take pleural biopsies. Excellent long-term results of pleurodesis have been reported after using talc – success rate of 82.1–92.7 [1,4,5]. Controversy exists, whether talc slurry can achieve similar results to talc insufflation. In two randomised studies equal results for both methods have been reported [6,7], however, in animal experiments talc insufflation gave significantly better pleurodesis compared to slurry [8]. The survey among English-speaking doctors reported better results for talc insufflation compared to other methods of pleurodesis [3]. Complications occurred in 28% of our patients. As previously reported in literature, fever was the most common adverse effect of talc pleurodesis [3,4]. We observed three cases of respiratory failure including one case of ARDS. ARDS is one of the most serious complications with intrapleural use of talc with a reported incidence between 1.3% [9] and even as high as 9% [10]. However, there have been large studies using talc where no cases of ARDS developed [1,5]. Administration of more than 5 g of talc has been suggested to be a risk factor for development of ARDS. Pleurodesis with a chemical agent induces pleural inflammation and production of pleural fluid, therefore post-operative pleural drainage seems to be mandatory to evacuate the fluid and achieve best approximation of pleural surfaces. In a recent study, rapid pleurodesis during less than 24 h of hospitalisation with only 2 h suction drainage has been proposed, but in that study effusion recurred more frequently compared to previous studies [11]. It has been also demonstrated in animal experiments that pleurodesis is more effective with pleural drainage [12]. In our study median duration of post-operative pleural drainage was 3 days. Previously, pleural drainage for 5.3±0.2 days has been reported after thoracoscopic talc pleurodesis, where in 6.1% of cases drainage time exceeded 7 days [4]. In our study, prolonged pleural fluid discharge and therefore prolonged pleural drainage for more than 7 days was observed in 12% of patients. For 13 patients bilateral talc pleurodesis was performed, and in 10 of the cases pleurodesis was performed as one operation during the same anaesthesia. Although, in fear of more complications, it has been suggested not to perform simultaneous bilateral pleurodesis, we observed similar morbidity and mortality after both uni- and simultaneous bilateral pleurodesis. Median survival after VATS talc pleurodesis in our patients was 8.4 months, which exceeds the median survival of 3.3 months recently reported in a study with a similar patient population [13]. In one of the previous studies median survival of 6.4 months has been reported for patients with thoracoscopic talc pleurodesis [4]. Better survival was observed among patients who responded to pleurodesis – 7.6 months versus 2.6 months of non-responders [4].
Burrows et al. prospectively investigated prognostic factors like pleural fluid pH, glucose, extent of pleural carcinomatosis and Karnofski performance status. The only predictor that achieved statistical significance was Karnofski score, no other variable correlated with survival [13]. Heffner et al. summarised data from previously published series and found that only pleural fluid pH has a modest predictive value for pleurodesis effectiveness and survival [2,14]. Patients with pleural fluid pH In our study we analysed survival of various primary cancers separately, but did not find any statistical difference (Fig. 2). Controversial results about the effect of pleural carcinomatosis extent on survival have been reported as well. Close (inverse) correlation between survival and the spread of tumorous lesions observed during thoracoscopy have been demonstrated, however, in the following update of the series similar correlation was not found [15]. We had six post-operative deaths. In all cases distant metastases besides pleura were present. Due to the retrospective nature of the study, we were not able to determine the performance status of all our patients. One can still assume that patients with metastases in multiple locations have worse performance status. According to our data multiple metastatic sites seem to be a risk factor for death after talc pleurodesis. Although several previous studies have tried to determine different prognostic factors for pleurodesis and survival of patients with a malignant pleural effusion, no definitive conclusions can be drawn at the moment. Nevertheless, even patients with shorter life expectancy and higher probability of pleurodesis failure need management of their recurrent pleural effusion to improve their quality of life. According to our results patients with multiple sites of metastases require less invasive treatment due to the high risk of post-operative mortality after talc pleurodesis. In other cases, after proper patient selection, reasonable survival can be expected after VATS talc pleurodesis.
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Abstract
1. Introduction
7.28 had significantly shorter survival compared to the patients with higher pleural fluid pH values. However, authors conclude that despite the correlation, pH has insufficient predictive accuracy for clinical use to identify patients, who should not undergo pleurodesis, because of poor short-term survival