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Ann Thorac Surg 2007;83:1940-1945
© 2007 The Society of Thoracic Surgeons

Original Articles: General Thoracic

Who Gains Most? A 10-Year Experience With 611 Thoracoscopic Talc Pleurodeses

Volker Steger, MDa,*, Ute Mikaa, Heikki Toomes, MDa, Tobias Walker, MDb, Corinna Engelc, Thomas Kyriss, MDa, Gerhard Ziemer, MDb, Godehard Friedel, MDa

a Department of Thoracic Surgery, Schillerhoehe Hospital, Gerlingen, Germany
b Department of Thoracic, Cardiac and Vascular Surgery, Tuebingen, Germany
c Institute for Medical Information Processing, University of Tuebingen, Tuebingen, Germany

Accepted for publication February 21, 2007.

* Address correspondence to Dr Steger, Department of Thoracic Surgery, Schillerhöhe Hospital, Solitudestr 18, 70839 Gerlingen, Germany (Email: vrsteger{at}gmx.de).


General thoracic surgery: The Annals of Thoracic Surgery CME Program is located online at http://cme.ctsnetjournals.org. To take the CME activity related to this article, you must have either an STS member or an individual non-member subscription to the journal.

 

   Abstract
Top
 Abstract
Introduction
 Patients and Methods
 Results
 Comment
 References
 
Background: Thoracoscopic talc pleurodesis is a therapeutic option for recurrent pleural effusion.

Methods: This retrospective study included 611 patients who underwent thoracoscopic talc pleurodesis between 1994 and 2003. We analyzed the risk factors, efficiency, outcome, follow-up, and survival, while taking into consideration primary disease and general condition.

Results: The mean follow-up was 319 days (range, 31 to 1994). A total of 105 (17.2%) of 611 patients died within 30 days after treatment. Risk factors for death within 30 days included a Karnofsky index of less than 50%, a body mass index of less than 25 kg/m2, malignant disease, and male gender. Treatment was successful in 347 (68.6%) of 506 patients, and 451 (89.1%) reported an improvement in symptoms. Previous thoracic irradiation and a chest tube drainage time exceeding 10 days negatively influenced the outcome of pleurodesis. The survival rate was negatively influenced by a preoperative Karnofsky index of less than 60% and by malignant disease.

Conclusions: Patients with pleural effusion due to malignant disease gain from early pleurodesis. The most favorable outcome after talc pleurodesis was seen in women whose lungs were fully expandable, in patients whose Karnofsky index exceeded 60%, in patients whose body mass index was greater than 25 kg/m2, and in patients with benign disease.

Pleural effusion is a frequent complication of disseminated or advanced malignant disease. Benign diseases such as congestive heart failure, renal insufficiency, and liver cirrhosis can also cause recurrent pleural effusion and result in severe restriction in quality of life. Patients experience dyspnea, cough, chest pain, and weight loss.

When therapy for the underlying disease is not possible, local treatment should be performed. The palliative treatment of choice is obliteration of the pleural space to prevent fluid accumulation. Options for local treatment of pleural effusion include therapeutic thoracocentesis, chemical pleurodesis, talc pleurodesis, pleural abrasion, parietal pleurectomy, and pleuroperitoneal shunt. Pleural talc pleurodesis is widely available, easy to perform, cost-effective, and efficient, which makes it the treatment of choice for recurrent malignant effusion [1–4].

Here we present our single-center experience with thoracoscopic talc pleurodesis during a span of 10 years. The goal of this study was to determine clinical predictors for successful thoracoscopic talc pleurodesis and to determine negative predictors for recurrences and mortality after pleurodesis. Risk factors, efficiency, outcome, long-term follow-up, and survival after thoracoscopic talc pleurodesis were analyzed, while taking into consideration primary disease, general condition, and clinical course.


   Patients and Methods
Top
 Abstract
 Introduction
 Patients and Methods
Results
 Comment
 References
 
The study was approved by the Ethics Committee of the University of Tübingen. According to the Ethics Committee, individual consent was not necessary because of the study’s retrospective design.

Patient Selection
The study population included all patients who received talcum pleurodesis between 1994 and 2003 at Schillerhoehe Hospital in Stuttgart-Gerlingen, Germany. More than 5000 thoracoscopic procedures were performed during this period, and 1030 patients underwent various forms of video-assisted pleurodesis: 182 had mechanical or thermic pleurodesis, and 216 had a pleurectomy. The study included 611 patients who underwent one procedure; excluded were 21 patients who had more than one talc pleurodesis.

Indications for talc pleurodesis included recurrent pleural effusion of malignant, benign, or unknown cause with at least one recurrence after thoracocentesis, or cytologically confirmed malignant effusion. Hospital records, personal data, and clinical course were analyzed retrospectively. Success was defined as full expansion of the lung at the end of the procedure, no recurrent pleural effusion in long-term follow-up, and no death within 30 days of the procedure.

Follow-Up
Patients who died within 30 days were analyzed for risk factors for early death. This included histology, malignant disease, Karnofsky index (KI) [5], and body mass index (BMI). The first outpatient follow-up took place 30 days after the intervention. An ultrasound examination and chest roentgenogram were performed to assess lung expansion and the presence or absence of effusion. Long-term follow-up included a questionnaire that was sent to the patient’s general practitioner or directly to the patient or relatives, or both, with questions concerning recurrences of effusion and symptoms. Some patients were questioned by phone.

Operative Technique
Pleurodesis was performed in all patients with a video-assisted thoracic surgical approach in a lateral position under general anesthesia. Double-lumen intubation and single-lung ventilation were used. A 10-mm thoracoscope with a 3-chip camera (Richard Wolf GmbH; Knittlingen, Germany) was used for video assistance. The first port insertion was guided by ultrasound imaging to prevent injury to the possibly adherent lung. The effusion was completely aspirated and preexisting adhesions were divided. Biopsy specimens of the pleura, lung, or mediastinal structures were taken when necessary for diagnostic purposes. Under visualization, up to 5 grams of asbestos-free talcum was applied evenly in the pleural space using an atomizer. Finally, a 28F chest tube was inserted through one of the port accesses. The chest tube was removed when the fluid loss was less than 150 mL in 24 hours and no air leakage was present.

Statistics
All statistical tests were performed by the Institute for Medical Information Processing at the University of Tübingen with SAS 8.0 software (SAS Institute, Cary, NC). Logistic regression was used to identify independent factors associated with successful pleurodesis and survival for more than 30 days after pleurodesis. To determine prognostic factors for survival, univariate and multivariate analyses were performed using the log-rank test and Cox regression model after verification of the proportional hazard assumption. Objective criteria for successful pleurodesis included a fully expanded lung at the end of the procedure and no recurrence of pleural effusion in long-term follow-up.

Survival rates were calculated using the Kaplan-Meier method. Duration of survival was defined as the time period between the date of pleurodesis and death. Patients who were still alive at the end of follow-up were excluded. Factors with p < 0.05 in the univariate testing were analyzed in a multivariate logistic regression or Cox regression model. The factors analyzed were primary disease (malignant versus benign, and breast cancer versus other malignant disease), age at operation, BMI at hospital admission (<25kg/m2 versus ≥ 25 kg/m2), preoperative KI (≤60% versus >60%, or ≤40% versus >40%), postoperative chest tube duration (≤10 days versus >10 days), previous thoracic irradiation, and gender.


   Results
Top
 Abstract
 Introduction
 Patients and Methods
 Results
Comment
 References
 
Study Population
A total of 611 patients (295 women, 316 men) with one-sided pleural effusion received thoracoscopic talc pleurodesis. Of these, 543 patients (88.9%) had malignant disease. After talc pleurodesis, 492 (80.5%) had a fully expanded lung, 451 (89.1%) had improvement in symptoms, and a recurrent pleural effusion developed in 135 (22.1%). A total of 105 patients (20.7%) died within the first 30 postoperative days, and 347 (68.6%) had a successful pleurodesis according to the criteria mentioned above. There were no cases of acute respiratory distress syndrome; however, 4 cases (0.6%) of empyemas and 2 cases (0.3%) of respiratory failure occurred, which were considered adverse effects of the pleurodesis. The study population’s demographic data and results are listed in Table 1.


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  		Table 1 Demographic Data and Results
 
Survival of at Least 30 Days
Patients with a KI of more than 40% had a 7.8 higher chance (odds ratio [OR]) of surviving more than 30 days after the procedure than did patients with a lower KI (p < 0.0001). Patients with a BMI of 25 kg/m2 or more (p = 0.0011; OR, 2.3) and patients with benign disease (p = 0.0546; OR, 2.5) had a more favorable survival rate. Of interest was that women had a 1.4 greater chance of surviving more than 30 days after pleurodesis (p = 0.0917) than did men, whereas age (p = 0.7213; OR, 0.996) and previous thoracic irradiation (p = 0.8772; OR, 0.950) did not influence 30-day-survival (Table 2).


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  		Table 2 Analysis of Risk Factors Influencing Survival Time of at Least 30 Days in 611 Patients
 
Success Rate of Talc Pleurodesis
The analysis of successful pleurodesis included 506 patients because the definition required the patients to have lived longer than 30 days after the procedure. By the definition, 347 patients (68.6%) had a successful pleurodesis. Patients with breast cancer had the lowest success rate at 68 (58.6%) of 116 compared with 47 (77%) of 61 in the group with benign disease (Table 1).

Chest tube duration exceeding 10 days (p < 0.0001) and previous ipsilateral thoracic irradiation (p = 0.0155) were risk factors for unsuccessful pleurodesis. Patients with chest tube duration exceeding 10 days had 3.0 times the risk of recurrent pleural effusion. Patients with previous ipsilateral irradiation had 1.9 times the risk of recurrence. The mean chest tube duration was 7 days (median, 5 days; Table 3).


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  		Table 3 Analysis of Risk Factors Influencing Long-Term Survival
 
Patients with a KI of less than 70% had 1.4 times the risk of unsuccessful pleurodesis, but this was not significant (p = 0.1187). The type of disease (p = 0.0984), BMI (p = 0.4242), and age at the time of surgery (p = 0.925) had no influence on pleurodesis success (ORs of about 1; Table 3). No correlation was found between the time between first diagnosis of malignant disease and successful pleurodesis (data not shown).

Long-Term Survival After Pleurodesis
Aside from preoperative KI (Fig 1), primary disease influenced the survival rate after thoracoscopic talc pleurodesis. Patients with benign disease had the highest 1-year survival rate at 78.5% compared with 33.4% for patients who had malignant tumors (Table 1). Patients with breast cancer had longer overall survival compared with all other malignant diseases (p = 0.0056, Fig 2). Primary lung cancer, pleural mesothelioma, other malignant diseases (p = 0.5024, data not shown), successful pleurodesis (p = 0.2725), chest tube duration (p = 0.9257), and age at surgery (p = 0.1590) did not influence survival.


Figure 1
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  		Fig 1. Survival analysis according to a Karnofsky index that exceeds 60% (solid line) compared with a Karnofsky index of 60% or less (dashed line; p < 0.0001).

 

Figure 2
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  		Fig 2. Survival analysis breast cancer (dashed line) compared with all other malignancies (solid line; p = 0.0056).

 
In a multivariate Cox regression model, only malignant disease showed a notable OR of 4.5, which meant the risk of death after pleurodesis was 4.5 times higher in patients with malignant disease (p < 0.0001; Fig 3). Patients with a KI of less than 60% (p = 0.0001) had a risk of death after pleurodesis 1.5 times higher than patients with a KI of 60% or more (Table 3).


Figure 3
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  		Fig 3. Survival analysis malignant disease (dashed line) compared with benign disease (solid line; p < 0.0001).

 

   Comment
Top
 Abstract
 Introduction
 Patients and Methods
 Results
 Comment
References
 
Malignancy is the most common cause of pleural effusion. The estimated number of patients with malignant pleural effusion may be as high as 100 per 100,000 population. This high incidence makes malignant pleural effusion a serious problem for health care institutions. Curative treatment in metastatic disease is usually impossible when the pleura are involved; thus, the goal of treatment for these patients is improvement in symptoms that worsen the quality of life.

Several methods have been investigated for treating malignant pleural effusion, including repeated needle aspiration, continuous pleural drainage with a thin-bore catheter and bag (which can be used for outpatients) [6, 7], pleurectomy [8], irradiation of the chest [9], intrapleural chemotherapy [10], chemoimmunotherapy [11], intrapleural {alpha}-2b interferon [12], antitumor necrosis factor [13], and transforming growth factor-ß2 [14]. Although these methods may be indicated under certain clinical conditions, the commonly used technique is chemical pleurodesis because of its simplicity, safety, and effectiveness.

The possibility of using talcum in pleurodesis as a supportive method in open lung surgery was first recognized by Bethune in 1935 [15]. The effect of talcum in pleurodesis is due to an interleukin-mediated influx of neutrophils and macrophages into the pleural space and consecutive activation of fibroblasts by mesothelial cells [16–18]. The talc pleurodesis as an independent therapeutical concept in malignant pleural effusion was first put into use by John Chambers in 1958 [19].

With video-assisted thoracoscopic techniques, pleural effusion can be removed completely under direct visualization and the agent for pleurodesis can be distributed equally in the pleural space. The goal is the obliteration of the pleural space to prevent recurrent effusion. Pleurodesis should not reduce the quality of life. It is well known that isolated thoracocentesis has no long-term benefit in the treatment of recurrent pleural effusions. Chest tubes, with or without chemical pleurodesis, do not show equivalent results compared with thoracoscopic techniques [20–23].

Patients with end-stage cancer have a reduced life expectancy. Until now, the benefit of talc pleurodesis was not clear. Life expectancy of more than 30 days without recurrent pleural effusion and relief of symptoms could be of great benefit for these patients. We found that patients with a BMI of 25 kg/m2 or more had a 2.3 times higher rate of surviving longer than 30 days after the procedure than did patients with a lower BMI. Patients with a KI of 50% or more had a 30-day survival rate eight times higher than patients with a lower KI, regardless of primary disease. In our institution, patients with symptomatic pleural effusion or mediastinal shift and poor general condition are treated with recurrent thoracocentesis or with a permanent indwelling chest tube drainage system as described by Putnam and colleagues [24].

We also found that the 30-day survival rate after thoracoscopic talc pleurodesis for women was 1.4 times higher than for men. According to our data, mortality can be reduced when careful consideration is given to the patient’s general condition before acceptance for thoracoscopic pleurodesis.

The superiority of the thoracoscopic technique compared with slurry application by chest tubes has already been proven by others [3, 4]. This is not only due to the more efficient distribution of talc in the pleural space but also because adhesions can be divided during the thoracoscopic procedure, which helps to release the contracted lung. Large biopsies of mediastinal and pleural tumors can be performed in the same setting when necessary.

Reports in the literature show there have been many attempts to perform pleurodesis using various chest tubes (small bore and regular tubes), with or without a sclerosing agent such as tetracycline, bleomycin, or doxycycline. Most of these studies had only a small number of patients (maximum of 60) [25, 26] and did not have information on long-term follow-up; therefore, evidence is limited. The efficiency rate of these studies, which mostly just analyzed selected cases, was between 25% and 80% [27–32]. Talcum was the only sclerosing agent that surpassed an 80% efficiency rate in a large series [33–36].

Results reported in the literature for talc pleurodesis show success rates of 90% to 94%. The overall success rate of 68.6% (347/506) in our study seems to be low. The range was between 58.6% (68/116) in breast cancer patients and 77% (47/107) in patients with benign disease. Improvement in symptoms was consistent at 89.1% (451/506).

One possible reason for the lower success rate could be the large number of consecutive, nonselected cases during the 10-year period. In addition, nearly 30% (151/506) of our patients had a preoperative KI of 60% or less, which by itself was associated with 1.4 times the risk for unsuccessful pleurodesis. Regression analyses did not prove to be significant (p = 0.1187, Table 4), however. These findings emphasize assumptions from Burrows and colleagues [37] that the preoperative KI is a reliable and strong predictor of successful pleurodesis.


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  		Table 4 Analysis of Risk Factors for a Nonsuccessful Pleurodesis
 
Another reason for the lower success rate could be due to the definition of long-term prevention of recurrences. Most reports on pleurodesis only include data on short periods of follow-up and do not provide information on long-term follow-up [33, 38–43]. In our study, 22.1% (135/611) of the patients had a recurrent pleural effusion, and 53% (71/135) had a recurrence between 30 and 612 days after the procedure.

Unlike other authors [44, 45], we found that previous ipsilateral thoracic irradiation decreased the success rate of talc pleurodesis (p = 0.0155). These patients had almost two times the risk of unsuccessful pleurodesis. Our results indicate that patients who have had thoracic irradiation should be carefully selected before being accepted for pleurodesis. Another clinical but not preoperative risk factor was chest tube duration of more than 10 days (p = 0.0001). This group had three times the risk for unsuccessful pleurodesis. This factor cannot be predicted in advance, unfortunately, but it can be helpful in making clinical decisions after the procedure.

Survival longer than 30 days, type of malignancy, and the KI had an influence on long-term survival. In terms of malignancy, patients with breast cancer had better survival rates than patients with other malignant disease. The KI was the strongest preoperative predictor for long-term survival (Table 3), a risk factor for hospital death (Table 2), and a valuable but not significant predictor for successful pleurodesis (Table 4).

Patients with recurrent pleural effusions, especially when caused by malignant disease, should be treated with thoracoscopic talc pleurodesis to improve symptoms and preserve quality of life. The procedure should be performed as early as possible, when the patient’s general condition is more favorable, because the aforementioned variables are associated with higher hospital mortality rates and shorter survival rates after pleurodesis.

Patients benefiting most from thoracoscopic talc pleurodesis are those who have a KI greater than 60%, a BMI greater than 25 kg/m2, those who have had no previous thoracic irradiation and who have a fully expandable lung.


   References
Top
 Abstract
 Introduction
 Patients and Methods
 Results
 Comment
 References
 

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