Malignant mesothelioma (MM) is a rare but incurable cancer of the pleura often linked to asbestos exposure. Although various treatment modalities from surgery to chemotherapy have been proposed for this malignancy, the majority of patients are treated with palliative intent. Chest wall pain and dyspnea, in association with progressive weight loss and fatigue, constitute the main symptoms experienced by patients afflicted with this condition.1
Pleural effusions are common in MM and methods to effectively relieve the associated respiratory symptoms are important in this disease. Unfortunately, traditional methods used in the palliation of malignant pleural effusions (MPE) may have lower success rates when applied to MM.2,3
The use of tunneled pleural catheters (TPC) has recently been described for the treatment of MPE4-7 and even advocated in MM.8 On the other hand, few patients with MM have been included in published TPC studies given the low prevalence of this cancer. This study was undertaken to assess the use of TPC in patients with MM treated in a single center with a large experience with the use of this approach.
This study is a retrospective analysis of a prospectively maintained, single-center database of TPC procedures. TPCs were introduced in our center in October 2001. A database of the first 250 procedures was developed is described elsewhere as is our clinical approach.9
Briefly, patients with recurrent symptomatic malignant pleural effusion were offered TPC treatment (Pleurx catheter; Denver Biomedical Inc., Golden, CO). TPCs were inserted under local anesthesia in the clinic (unless already admitted to hospital) without ultrasound guidance in the large majority of cases. Catheters were initially drained 3 times per week using 1 or 2 bottles (550 mL each) by palliative home care nurses and/or by patients and their family. Volume and frequency of drainage were adjusted according to symptoms and radiologic findings at follow up. Patients were scheduled for a follow-up visit and chest x-ray (CXR) at 2 weeks and then every 6 to 8 weeks thereafter and on an as-needed basis. Patients were followed until TPC removal or death. TPCs were removed once drainage was less than 50 mL during 3 sequential drainage attempts and fluid reaccumulation was not detected on CXR (Fig. 1).
The database includes the following information: patient identification, gender, age, primary malignancy, size of effusion on pretreatment CXR, side of effusion, dates of insertion, removal, death (if known), complications, symptom control at 2-week follow up (complete, partial, absent), size of effusion on CXR 2 weeks postprocedure, ipsilateral pleural procedures before TPC, ipsilateral pleural procedures after TPC treatment, contralateral TPC placement, and date of last follow-up visit at the cancer center if still alive.
All dates were calculated from the day of TPC insertion. Spontaneous pleurodesis (SP) was said to occur when drainage decreased to less than 50 mL of fluid for 3 consecutive drainage attempts without progressive symptoms or reaccumulation of fluid on CXR. Date of SP was calculated according to date of TPC removal and not date on which fluid stopped draining. Dyspnea control was prospectively determined at 2-week follow-up evaluation and described on a simple 3-point scale as complete if the patient noted the absence or minimal presence of symptoms, partial if the patient described significantly improved but persistent dyspnea, and absent if no significant improvement of dyspnea was noted. We did not differentiate between other contributing causes of dyspnea (pleural peel, emphysema, and so on) unless there was complete reexpansion of the lung and absence of residual fluid.
Size of effusion was analyzed visually by one of the investigators as a fraction of the hemithorax filled with fluid on a standard posteroanterior and lateral CXR before TPC insertion and at the 2-week follow-up visit. The patient was deemed to have an adequately reexpanded lung if 20% or less of the treated hemithorax contained fluid at 2 weeks. Patients who had undergone the following procedures before TPC were considered to have received “significant prior treatment”: more than 2 therapeutic thoracentesis, chest tube, chemical pleurodesis, thoracoscopy, or prior TPC. Complications as well as any ipsilateral pleural procedures required post-TPC placement were recorded as well.
All data was entered in spreadsheet format in a statistical computer software program (SPSS version 13.0). Procedures in the database were separated in 2 groups according to diagnosis of MM or other, which was used as the control group (CG) in the analysis. Descriptive statistics were used to summarize patient characteristics, SP rates, symptom control rate, size of effusion, complication rates, and repeat procedures.
Comparisons between the MM and CG group were performed considering a P value of less than 0.05 as statistically significant. The t test was used to compare continuous variables between the 2 groups. Impact of nominal factors on symptom control, SP, and complications were assessed with chi-squared test or Fisher exact test as appropriate. Survival data were analyzed using the Kaplan-Meier method and comparisons determined with the Breslow method.
Between November 2001 and May 2004, 31 TPC procedures were attempted in 26 patients with MM (2 contralateral and 3 repeat ipsilateral procedures). Two patients included in the MM group had high suspicion of MM based on clinical, radiologic, and noninvasive pleural findings, but further invasive testing was declined. Mean age was 70.8 years (range, 50-86 years), and 2 of the 26 patients were female. At the time of analysis, all patients had the TPC removed or had died with it in place. The CG group comprised of 195 patients undergoing 218 TPC insertions (17 contralateral and 6 ipsilateral). The CG was significantly younger with a mean age of 63.4 years (range, 33-90 years) and included more females (56.4%) than the MM group. Tumor cell types in the CG were nonsmall cell lung cancer in 42.2%, breast cancer in 22.5%, ovarian cancer in 8.7%, and other in 26.6%.
Insertion was considered unsuccessful in 2 patients, because in both cases, less than 250 mL of fluid was removed postinsertion despite intrapleural placement confirmed on x-ray, leading us to remove the catheter because significant benefit seemed unlikely. Dyspnea control at the 2-week follow-up visit in the MM group was found to be complete after 12 (38.7%) procedures and partial after 17 (54.8%), whereas 2 (6.5%) procedures were failed insertions. No significant differences in dyspnea control were noted between the MM and CG groups.
Spontaneous pleurodesis occurred after 12 of 31 (38.7%) insertions and in 8 of 15 (53.3%) procedures, resulting in less than 20% of residual effusion at the 2-week follow-up x-ray. These findings were not statistically different than for the CG.
The TPC remained in place until removal or death for a median of 83 days (95% confidence interval [CI], 59.0-107.0) with 14 catheters in place until death. This was longer than in the CG in which the TPC was in place for 52 days (95% CI, 42.3-61.6; P < 0.05 Breslow test) and is likely the result of longer survival in the MM group (see subsequently). In patients achieving SP, the median time to catheter removal was 77 days (95% CI, 22.7-131.3) with no difference seen with the CG.
Repeat pleural procedures were required after 4 (12.9%) TPC procedures for MM (3 repeat TPC and 1 thoracentesis). The 3 repeat TPCs were as follows: 1 patient had previously experienced a failed insertion; another's catheter stopped draining but he was symptomatic with loculated fluid; and a third patient's catheter cuff was dislodged after a cellulitis at the insertion site. Only 1 repeat procedure (thoracentesis for 300 mL before development of chest tightness) was performed after 12 episodes of SP (8.3%), similar to our observations in the CG.
Total and specific number of complications was similar between the MM and CG group and were as follows: pneumothorax/bronchopleural fistula (2), unsuccessful insertion (2), empyema (2), cellulitis (1), fluid loculation (2), dislodged catheter (1), and bleeding (1).
The median survival for MM and CG was 203 days (95% CI, 167.6-238.4) and 130 days (95% CI, 101.9-158.1), respectively, but this difference was not statistically significant.
Given the incurable nature of MM, simple, effective, and minimally invasive methods to palliate symptoms associated with this disease would be of great benefit. Whereas chemotherapy has recently been shown to offer modest survival benefit10 in this disease, no surgical approach has been proven to improved survival in a controlled study setting.1
Dyspnea is a presenting symptom in almost half of all patients11 and is a frequent problem in the majority of patients as the disease progresses. Palliative approaches to dyspnea in mesothelioma have included surgical pleurectomy or decortication,12-18 thoracoscopic pleurodesis3,19,20 or chemical pleurodesis through a chest tube.21 We now report our experience using TPC for palliation of dyspnea in pleural effusion caused by MM.
Given the lack of comparative trials between any of these approaches in MM, and the rare trials in MPE in general, it is difficult to make direct comparisons between retrospective case series done in different countries, in different patient populations, and without clear selection criteria for selecting a particular treatment of a given patient.
One of the advantages of TPC over other more invasive methods of palliation for MPE is the limited contraindications to the procedure, so that patients with poor performance status, severe comorbidities, and trapped lung may still be offered effective palliation. Given the lack of impact on survival from any of these palliative therapies, observations of survival rates in different series allows one to comment on the degree of selection that occurred in application of a given treatment. For example, median survivals of 16 (2), 17 (17), and 19 months (1) in patients with MM suggests that very selected patients were treated in these studies given the typical overall median survival for MM of 7 months.11 The median survival for our cohort of 6.8 months suggests that this group of patients was fairly representative of patients with MM.
Symptom control should be the main goal of treatment of MPE. The majority (93.7%) of patients with MM treated with TPC had improvement in dyspnea. The degree of symptom relief is difficult to quantify more precisely and compare between studies given that objective dyspnea scores were not measured in any study concerning treatment of pleural effusions in MM. The use of more detailed dyspnea and symptom scores as well as quality-of-life instruments should be encouraged for future studies. Extrapolating from other MPE studies, data from a randomized trial does suggest that the use of TPCs lead to equivalent symptom control as pleurodesis.7
If one accepts that TPC can lead to similar symptom control than other methods, choosing the method of choice would involve issues such as impact of overall quality of life, invasiveness, complication rates, and cost. The possibility of offering a simple, outpatient method to control MPE is likely to lead to better quality of life and reduced costs. Hospital length of stay for pleurectomy/decortication or thoracoscopic pleurodesis is rarely reported in publications, despite frequent claims for the “short” hospital stay requirement after these procedures.
Complications after pleural interventions are not unexpected, but the number and severity of complications seen after TPC seem favorable when compared with other modalities. Empyema occurred after 6.25% of our procedures, similar to the 6% rate seen in a large series of patients with MM treated with pleurectomy/decortication, but somewhat higher than the 2.5% rate seen after thoracoscopic talc poudrage,3 although this latter study did not describe complications separately for patients with MM who comprised 24% of the patients studied. This may be of importance because our empyema rate overall in non-MM MPE patients treated with TPC appears lower than the rates seen in MM (2.8% vs. 6.25%, not statistically significant). We cannot know if this higher rate is simply a statistical anomaly or if the nature of MM places patients at higher risk for empyema after pleural interventions. The patients with MM did live longer than the CG with the catheter in place, which may also increase the risk of developing empyema, although the number of infection per 1000 catheter days also trended higher (0.6 vs. 0.2 per 1000 catheter days, not significant) in the MM group. Our incidence of air leaks was also significant (6.5%) but in the low range of the 6% to 12% incidence of prolonged air leak seen with other techniques.3,17 We believe that air leaks noted are not the result of lung injury at the time of placement, but the result of visceral pleural tears during reexpansion, because this complication usually occurs several days after placement of the TPC. Other significant postprocedure complications, as seen in a recent trial of talc pleurodesis through chest drain or thoracoscopy22 such as fever, atelectasis, pneumonia, respiratory failure, dysrhythmia, and treatment-related deaths can be avoided by using a TPC instead of a more invasive modality.
No long-term cost analysis has been performed for TPC. Although one study documented short-term cost benefit of TPC use,6 the main cost of this modality involves home drainage supplies, which were not factored into this study. Nevertheless, avoidance of need for inpatient hospital and operating room resources is likely to favor TPC even in the long term.
In summary, the use of TPC offers a rapid, effective, and minimally invasive method to palliate dyspnea in patients with MM on an outpatient basis and with few contraindications. Although local complications may be slightly higher than in other patients with MPE, these remain acceptable, manageable, and compare favorably with those seen with other treatment modalities.
1. Pistolesi M, Rusthoven J. Malignant pleural mesothelioma
: update, current management, and newer therapeutic strategies. Chest
2. Sterman DH, Kaiser LR, Albelda SM. Advances in the treatment of malignant pleural mesothelioma
3. Viallat JR, Rey F, Astoul P, et al. Thoracoscopic talc poudrage pleurodesis
for malignant effusions. A review of 360 cases. Chest
4. Musani AI, Haas AR, Seijo L, et al. Outpatient management of malignant pleural effusions with small-bore, tunneled pleural catheters. Respiration (Herrlisheim)
5. Pollak JSM. Treatment of malignant pleural effusions with tunneled long-term drainage catheters. J Vasc Interv Radiol
6. Putnam JB Jr, Walsh GL, Swisher SG, et al. Outpatient management of malignant pleural effusion
by a chronic indwelling pleural catheter. Ann Thorac Surg
7. Putnam JB Jr, Light RW, Rodriguez RM, et al. A randomized comparison of indwelling pleural catheter and doxycycline pleurodesis
in the management of malignant pleural effusions. Cancer
8. Seijo L, Sterman D. Treatment of mesotheliomatous pleural effusion
: experimental therapy versus thoracoscopic talc poudrage? Pro: experimental therapy. Journal of Bronchology
9. Tremblay A, Michaud G. Single center experience with 250 tunnelled pleural catheter insertions for malignant pleural effusion
. 2005 (In press).
10. Vogelzang NJ, Rusthoven JJ, Symanowski J, et al. Phase III study of pemetrexed in combination with cisplatin versus cisplatin alone in patients with malignant pleural mesothelioma
. J Clin Oncol
11. Merritt N, Blewett CJ, Miller JD, et al. Survival after conservative (palliative) management of pleural malignant mesothelioma
. J Surg Oncol
12. Brancatisano RP, Joseph MG, McCaughan BC. Pleurectomy for mesothelioma
. Med J Aust
. 1991;154:455-457, 460.
13. Canto A. Videothoracoscopy in the diagnosis and treatment of malignant pleural mesothelioma
with associated pleural effusions. Thorac Cardiovasc Surg
14. Colaut F, Toniolo L, Vicario G, et al. Pleurectomy/decortication plus chemotherapy: outcomes of 40 cases of malignant pleural mesothelioma
. Chir Ital
15. Grossebner MW, Arifi AA, Goddard M, et al. Mesothelioma
-VATS biopsy and lung mobilization improves diagnosis and palliation. Eur J Cardiothorac Surg
16. Martin-Ucar AE, Edwards JG, Rengajaran A, et al. Palliative surgical debulking in malignant mesothelioma
. Predictors of survival and symptom control. Eur J Cardiothorac Surg
17. Soysal O, Karaoglanoglu N, Demiracan S, et al. Pleurectomy/decortication for palliation in malignant pleural mesothelioma
: results of surgery. Eur J Cardiothorac Surg
18. Waller DA, Morritt GN, Forty J. Video-assisted thoracoscopic pleurectomy in the management of malignant pleural effusion
19. Aelony Y. Treatment of mesotheliomatous pleural effusion
. Pro: talc poudrage therapy. Journal of Bronchology
20. de Campos JRM, Vargas FS, Werebe EC, et al. Thoracoscopy talc poudrage: a 15-year experience. Chest
21. Senyigit A, Bayram H, Babayigit C, et al. Comparison of the effectiveness of some pleural sclerosing agents used for control of effusions in malignant pleural mesothelioma
: a review of 117 cases. Respiration (Herrlisheim)
22. Dresler CM, Olak J, Herndon JE, et al. Phase III intergroup study of talc poudrage vs talc slurry sclerosis for malignant pleural effusion