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Thoracoscopic Talc Versus Tunneled Pleural Catheters for Palliation of Malignant Pleural Effusions
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.
Thoracoscopic Talc Versus Tunneled Pleural Catheters for Palliation of Malignant Pleural Effusions Ben M. Hunt, MD, Alexander S. Farivar, MD, Eric Vallières, MD, Brian E. Louie, MD, Ralph W. Aye, MD, Eva E. Flores, LPN, and Jed A. Gorden, MD Division of Thoracic Surgery and Interventional Pulmonology, Center for Pleural Diseases, Swedish Cancer Institute, Swedish Medical Center, Seattle, Washington
Background. A malignant pleural effusion (MPE) is a late complication of malignancy that affects respiratory function and quality of life. A strategy for palliation of the symptoms caused by MPE should permanently control fluid accumulation, preclude any need for reintervention, and limit hospital length of stay (LOS). We compared video-assisted thorascopic (VATS) talc insufflation with placement of a tunneled pleural catheter (TPC) to assess which intervention better met these palliative goals. Methods. We conducted a retrospective chart review of consecutive MPE at a single institution from 2005 through June 2011. Primary a priori outcomes were reintervention in the ipsilateral hemithorax, postprocedure LOS, and overall LOS. Results. One hundred nine patients with MPE were identified. Fifty-nine patients (54%) had TPC placed, and 50 (46%) were treated with VATS talc. Patients who underwent TPC placement had significantly fewer rein-
terventions for recurrent ipsilateral effusions than patients treated with VATS talc (TPC 2% [1 of 59], talc 16% [8 of 50], p ⴝ 0.01). Patients treated with TPC had significantly shorter overall LOS (TPC LOS mean 7 days, mode 1 day; talc mean 8 day, mode 4 days, p ⴝ 0.006) and postprocedure LOS (TPC post-procedure LOS mean 3 days, mode 0 days; talc mean 6 days, mode 3 days, p < 0.001). Type of procedure was not associated with differences in complication rate (TPC 5% [3 of 59], talc 14% [7 of 50], p ⴝ 0.18), or in-hospital mortality (TPC 3% [2 of 59], talc 8% [4 of 50], p ⴝ 0.41). Conclusions. TPC placement was associated with a significantly reduced postprocedure and overall LOS compared with VATS talc. Also, TPC placement was associated with significantly fewer ipsilateral reinterventions. Placement of TPC should be considered for palliation of MPE-associated symptoms. (Ann Thorac Surg 2012;94:1053–9) © 2012 by The Society of Thoracic Surgeons
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Several options exist for the treatment of MPE. The most common strategies are thoracentesis, pleurodesis, and placement of a tunneled pleural catheter (TPC). Thoracentesis is primarily a diagnostic procedure, and often also results in transient relief of symptoms [7, 8]. Pleurodesis may be attempted for recurrent symptomatic pleural effusions, either through a thoracostomy tube or during videoassisted thorascopy (VATS) [9]. Pleurodesis has a high success rate in selected patients (75% to 95%) [2, 9 –12], but it is an invasive procedure that requires hospitalization, has associated morbidity, and can be painful. Pleurodesis is not usually effective if the lung does not fully reexpand when the effusion is evacuated [7, 13–15]. The TPC can be used independent of the degree of lung expansion and can be managed by the patient or a designated caregiver [16 –18]. However, TPCs require ongoing drainage to manage the effusion and a support infrastructure to assist with drainage and supplies.
alignant pleural effusion (MPE) is an end-stage manifestation of many cancers [1]. The annual incidence of MPE in the United States has been estimated between 150,000 and 200,000 [1, 2]. Patients with MPE have a median survival of 4 to 6 months [3, 4]. Because MPE is associated with advanced malignancy, treatment is focused on palliating symptoms rather than cure. The ideal palliative procedure has a short length of stay (LOS), minimal future requirements for interaction with the medical system, good efficacy, and minimal postprocedure pain or complications [5, 6]. Accepted for publication Jan 11, 2012. Presented at the Fifty-eighth Annual Meeting of the Southern Thoracic Surgical Association, San Antonio, TX, Nov 9 –12, 2011. Address correspondence to Dr Gorden, Center for Pleural Diseases, Division of Interventional Pulmonology, Swedish Cancer Institute, Swedish Medical Center, 1101 Madison St, Ste 850, Seattle, WA 98104; e-mail: [email protected].
© 2012 by The Society of Thoracic Surgeons Published by Elsevier Inc
0003-4975/$36.00 doi:10.1016/j.athoracsur.2012.01.103
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Every option for the palliation of MPE-associated symptoms has potential disadvantages, and no one strategy is appropriate for every patient. The challenge is to select the appropriate management strategy for each individual patient, bearing in mind the goals of palliation. Because we currently employ several different strategies for the treatment of MPE, we performed a retrospective review of our management of MPE at a single institution to determine which strategy best achieved our palliative goals.
Patients and Methods A retrospective chart review was performed at a single institution from 2005 to June 2011. Patients were identified by a database query for International Classification of Diseases, Ninth Revision codes for VATS with pleurodesis (32650), TPC placement (32550), and chemical pleurodesis (32560). Because bedside pleurodesis by talc slurry is usually performed by residents without an attending present at our institution, bedside pleurodesis was not billable and was not identified by our query. Identified patient charts were reviewed to confirm the diagnosis of MPE and to abstract data on demographics, LOS, complications, inhospital mortality, cancer type, and repeat procedures on the ipsilateral hemithorax. A priori primary outcomes were overall LOS, LOS after the procedure, and ipsilateral reintervention. Secondary endpoints were complications, inhospital mortality, and hospital readmission for an ipsilateral effusion. Because many patients with MPE were hospitalized for other reasons before having a procedure to address the effusion, we analyzed both overall LOS and postprocedure LOS. The Institutional Review Board of Swedish Medical Center approved this study and waived the requirement for informed consent owing to the study’s retrospective nature. All patients in the VATS talc group had reexpansion of the lung at surgery. Four grams of aerosolized talc were insufflated into the chest under direct VATS observation. After VATS talc pleurodesis, a chest tube was placed, kept on 20 cm H2O suction for 48 hours, and then maintained on water seal until drainage dropped below 200 mL per day. Patients were normally discharged on the same day their chest tube was removed. Chest radiographs were obtained in the recovery room, daily while the chest tube was in place, and after chest tube removal. The TPCs used in this series were all PleurX catheters (CareFusion, San Diego, CA). The TPCs were either placed percutaneously using conscious sedation or at the time of VATS if VATS was required for another indication (such as pleural biopsies or a pericardial window). Additionally, if VATS talc was planned and the lung did not reexpand at the time of surgery, pleurodesis was not performed, and a TPC was placed instead. Before TPC placement, it was confirmed that the patient’s symptoms improved after removal of the effusion by thoracentesis. Potential candidates for TPC placement view an educational video and have an educational session conducted by a nurse or an interventional pulmonologist preoperatively. Care is taken to ensure that the patient’s insurance will cover the drainage supplies before insertion of the TPC. After TPC place-
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Table 1. Patient Demographics and Cancer Types Demographic Sex Female Male Mean age, years Cancer Type Lung Mesothelioma Breast Ovarian Gastrointestinal Other
TPC (n ⫽ 59)
Talc (n ⫽ 50)
p Value
38 (64%) 21 (36%)
27 (54%) 23 (46%)
0.36 0.36
66
66
0.95
TPC (n ⫽ 59)
Talc (n ⫽ 50)
Combined
27 (46%) 5 (8%) 10 (17%) 11 (19%) 2 (3%) 4 (7%)
15 (30%) 15 (30%) 5 (10%) 4 (8%) 6 (12%) 5 (10%)
42 (39%) 20 (18%) 15 (14%) 15 (14%) 8 (7%) 9 (8%)
TPC ⫽ tunneled pleural catheter.
ment, patients and their caregivers are taught to drain the TPC in a hands-on session. Catheters are then drained on a schedule that is individualized for each patient. The tests used for statistical comparisons were as follows: the t test for normally distributed continuous variables, the Mann-Whitney-Wilcoxon test for continuous variables with nonnormal distribution, Pearson’s 2 test with Yates’ continuity correction for discrete variables, and Fisher’s exact test for discrete variables with cell frequencies too low for the 2 test. All p values were two-tailed, and no adjustments were made for multiple comparisons. A p value less than 0.05 was considered statistically significant. All statistical analyses were performed using R software (available at: www.r-project.org).
Results One hundred nine consecutive patients with MPE were identified; TPCs were placed in 59 of 109 patients (54%), and 50 of 109 patients (46%) underwent VATS talc pleurodesis. Of the TPCs, 47 of 59 (80%) were placed using conscious sedation by the Seldinger technique, and 12 of 59 (20%) were placed during VATS. All talc pleurodeses in this series were done by VATS. One VATS talc case was converted to open to control bleeding from pleural biopsies (2% conversion rate). Patient demographics and cancer type (Table 1) were similar between the groups. With respect to primary endpoints, patients had shorter overall hospital LOS after TPC placement than VATS pleurodesis (Table 2). Postprocedure LOS was also significantly shorter after TPC placement (Table 2, Fig 1). Additionally, patients who underwent TPC placement had significantly fewer reinterventions for recurrent ipsilateral effusions (Table 2). Postprocedure complications were not significantly different between the two groups (Table 2). The following complications occurred: 1 patient who had a TPC placed by Seldinger technique had an empyema; 1 patient had respiratory failure and died after VATS for pleural biopsies and TPC placement; another patient had intraoperative bleeding after pleural biopsies as part of a VATS TPC placement;
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Table 2. Comparison Between Tunneled Pleural Catheter and Video-Assisted Thoracic Surgery Talc in Management of Malignant Pleural Effusion Variables LOS, days Mean Mode Postprocedure LOS, days Mean Mode Reintervention Complications Readmission for ipsilateral effusion In-hospital mortality LOS ⫽ length of stay;
TPC (n ⫽ 59)
Talc (n ⫽ 50)
p Value
7 1
8 4
0.006
3 0 1 (2%) 3 (5%) 7 (12%)
6 3 8 (16%) 7 (14%) 6 (12%)
⬍ 0.0001
2 (3%)
4 (8%)
0.41
0.01 0.18 0.78
TPC ⫽ tunneled pleural catheter.
and the following complications occurred after VATS Talc, each in 1 patient: acute respiratory distress syndrome, exacerbation of hepatic encephalopathy, hypoxia requiring home oxygen, intraoperative bleeding after pleural biopsies, empyema, wound dehiscence, and atrial fibrillation. There was no difference in the rate of hospital readmission for ipsilateral pleural effusion (Table 2). The type of procedure was not associated with a significant difference in in-hospital mortality (Table 2).
Comment Malignant pleural effusion significantly affects patient quality of life [1, 2]. Currently, several options exist for the treatment of MPE (Table 3). Most published guidelines for management of MPE begin with a recommendation for thoracentesis, which provides diagnostic and therapeutic value [1, 7, 13, 14]. Thoracentesis evaluates lung entrapment and whether symptoms are relieved by draining the effusion. Both are critical branch points when evaluating future palliative options [7]. If the MPE recurs, a definitive palliative strategy should be considered. Chemical pleurodesis is the traditional pro-
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Table 3. Strategies for Managing Malignant Pleural Effusion Observation Palliation with oxygen and narcotics Serial thoracentesis Tunneled pleural catheter Bedside pleurodesis through a chest tube Pleurodesis at thoracoscopy
cedure used to treat recurrent MPE [19, 20]. Pleurodesis attempts to achieve fusion of the visceral and parietal pleura and requires lung reexpansion [13]. The disadvantages of pleurodesis relate to pain and the requirement for hospitalization [2]. The Cancer and Leukemia Group B (CALGB) 9334 trial did not find a difference in overall pleurodesis rate between VATS talc and talc slurry by chest tube, but a post-hoc subgroup analysis favored VATS in patients with near-complete lung reexpansion and in patients with breast and lung cancers [9]. The higher pleurodesis rate after VATS was also seen in a Cochrane review that predates the CALGB trial [21]. Many agents have been used to fuse the pleural space, including talc, povidoneiodine, doxycycline, dextrose, and other sclerosants [21]. Talc was clearly favored over other sclerosants in a Cochrane review [21]. Pulmonary complications with talc pleurodesis have been reported including the development of acute respiratory distress syndrome [22, 23]. Various approaches have been tried to mitigate the morbidity of pleurodesis [24, 25], but it still requires a hospital stay, is a painful procedure, and is not useful unless the lung fully reexpands when the effusion is drained. The TPC was approved by the Food and Drug Administration for managing recurrent MPE in 1997 [26], and TPCs are increasingly used for this indication. They are the preferred palliative method for patients with lung entrapment [16 –18]. The minimally invasive nature of the TPC allows it to be placed for palliation in a wide range of patients with varying performance status, and a TPC does not require lung expansion to achieve palliation. The TPC can be placed in the outpatient ambulatory setting [27, 28]. Good symptom control has been reported in large series of patients treated with TPCs [27], and our series confirms that Fig 1. Postprocedure length of stay (LOS) after video-assisted thorascopic (VATS) talc (white bars) and tunneled pleural catheter (TPC) placement (black bars).
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Fig 2. Proposed management strategy for management of pleural effusions in patients with cancer. (CXR ⫽ chest radiograph; TPC ⫽ tunneled pleural catheter.)
TPCs can be placed with acceptable rates of morbidity and in-hospital mortality. Although TPCs can achieve pleurodesis in as many as 72% of selected patients [29], this population cannot be identified a priori, and most patients will require lifelong serial drainage [18, 27, 30]. Like any indwelling device, they carry a risk of infection; the incidence of empyema with TPCs has been reported from 2% to 12% [5, 18, 27, 31] and was 2% in this study. Lastly, and importantly, the implantation of a TPC must be considered a program and not simply a procedure. A clinical infrastructure must be created to support patients and their caregivers, who will require preprocedure counseling, insurance assistance, and postprocedure education and support. For a frail, end-stage population, we conclude that TPCs afforded better palliation than VATS talc by our criteria, because patients had shorter overall hospitalizations and shorter postprocedure length of stay. The TPC resulted in fewer ipsilateral reinterventions when compared with VATS talc, thus requiring fewer interactions with the health care system. These findings suggest TPC placement may be more optimal than pleurodesis for palliation in patients who have a poor prognosis and a short expected lifespan.
It remains unclear whether pleurodesis or TPC is a better option for palliation of symptoms in patients who do not have lung entrapment, have a good performance status, and have a relatively long life expectancy. Cost analysis studies have favored pleurodesis for patients with longer life expectancy [32, 33]. The TPC was found to have a similar success rate with a shorter hospital stay when compared with doxycycline pleurodesis [16]. The CALGB 30102 trial randomly allocated 58 patients with MPE to talc slurry pleurodesis or TPC, and TPC had higher technical success, better dyspnea scores, and performed better on the composite endpoint of death or effusion recurrence, but the trial was stopped early owing to insufficient accrual [34]. Thus far, VATS talc pleurodesis has not been compared with TPC in a prospective, randomized setting. Our current algorithm for management of MPE is presented in Figure 2. This case series is limited by its retrospective nature. We did not capture data on symptoms, cost, comorbidities, or functional status. An additional inherent limitation is patient selection bias. Although this series is neither controlled nor randomized, it provides evidence that patients with MPE treated with TPC needed fewer reinterventions
and were out of the hospital sooner than the patients who underwent VATS talc pleurodesis. Any treatment strategy for MPE must be evaluated with respect to palliative goals: limiting hospitalizations, procedures, and pain while providing durable symptom control. In patients with poor performance status, palliation can be achieved with the low-risk outpatient placement of a TPC. For patients with longer life expectancy and better performance status, it remains an individual decision between the provider and the educated patient whether to perform pleurodesis or place a TPC. Further prospective studies are required to validate the decisionmaking algorithm presented here. The authors would like to acknowledge the support of the Ryan Hill Foundation.
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16.
17. 18.
19. 20. 21. 22.
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DISCUSSION DR TODD L. DEMMY (Buffalo, NY): Nice presentation, Ben. Thank you for the manuscript. The optimal therapy for malignant pleural effusions is controversial, and it is surprising that it is an understudied problem despite how commonplace it is for
thoracic surgeons. Study accrual can be challenging for these patients who are distressed by their dyspnea and have limited life expectancy despite this palliative intervention. In CALGB 30102, 57 patients were randomized between a primarily outpa-
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tient procedure, that is, the PleurX or the tunneled catheter, versus an inpatient talc slurry, and this study was closed early for slow accrual. But like your study, we saw that there was better effusion control at 1 month with the tunneled catheter, and we found that the symptom control correlated well with persistence of lung expansion. This leads to question number one. The tunneled catheter was intended to be an outpatient procedure and yet about 60% of your patients had a postoperative stay of 1 day in the hospital. Please comment further on your rationale to use this as an inpatient therapy and tell us if any patients had outpatient catheter placement. In a similar vein, also comment on why no patients had talc delivered by chest tube slurry given its equivalence to VATS talc in CALGB 9334. And lastly, question number two relates to the algorithm that you just showed that recommends either talc or a tunneled catheter for the full expanders. Since your pooled survival analysis favors talc is biased by the greater number of mesothelioma patients in this group and the fewer number of trapped lungs in this cohort, have you tried to use case matching, propensity scores, or something similar to that to compare those outcomes? In particular, have you analyzed just the outcomes of the group that had full expansion in this study?
patient. Some people don’t want a tube hanging out of their side for 3 months, and so it is an easy decision. But I think the one thing you have underplayed is that box about the pleural biopsy. I can’t tell you how now genomics has changed our practice over the past few years. I have been sending our tumors for genetic testing for 4 or 5 years now, but the oncologists were not interested—now everyone wants to see “the tumor biology”—like it is some new concept. We are doing more mediastinoscopies than EBUS and EUS, because we want to get EML ALK4s, we want to get EGFR and PTEN, and so forth. It is the same thing here. I can’t tell you how many patients we have who have been told they have metastatic lung cancer by cytology, but you put a scope in and you biopsy it, and they are ER/PR positive for metastatic breast cancer—real information that will change their therapy. So I think when you do your study, you need to include the fact that with a VATS and a pleural biopsy you get a lot more information and you put patients on an oral or more gentle and efficacious chemotherapy. Although they have a short duration of life, oral chemotherapy may improve their quality of life. So, do you have any comments on how it affected their care, not just with securing the diagnosis but also in getting genomics and guided therapy?
DR HUNT: Thanks for your comments and questions. In regard to the 60% of patients who had a 1-day hospital stay, that is strictly an issue of nomenclature. Those patients were treated on an outpatient basis, and we counted the 1 day as the day the procedure was performed. So that’s a little bit confusing. But that 1-day stay is the day that the procedure was performed. Then you asked about talc slurry versus VATS talc. We do perform talc slurry in some patients at our institution; however, we did not include those patients in this analysis. It was difficult to pull those charts retrospectively based on simply a codebased query. But since a lot of the patients we see have either lung or breast cancer, which was a subset that did better with VATS talc than talc slurry through chest tube in the CALGB trial you performed, we do tend to favor VATS talc in those patients who are able to undergo the procedure.
DR HUNT: Thanks for the comment. We agree completely that the goal in these patients is to palliate their symptoms and then limit their interaction with the medical system as much as possible. So in those cases when pleural biopsies would definitively change management, we favored pleural biopsy, but if the oncologist wasn’t going to change management based on the results of the pleural biopsy, then we usually did not perform VATS because of its associated complications.
DR DEMMY: The other question was regarding patients whose lungs can expand fully— did you look at that group alone? This is because your survival curves are biased by the larger proportion of mesothelioma patients for the talc and the trapped lungs in the tunneled catheter groups. DR HUNT: We did not look at those patients who had complete reexpansion of their lungs versus those patients who did not have complete reexpansion. We intended to go after those data, but from the operation notes and review of the hospital records, we couldn’t tease out which patients had complete reexpansion of their lungs. All these are very good points; they are clear limitations of a retrospective study, and so we together with CALGB would like to perform a prospective study comparing VATS talc with tunneled pleural catheters, because we think this is an important question that faces a lot of thoracic surgeons. In these patients with good performance status with a long life expectancy with a lot of options for treating their cancer, are patients better served by placing a tunneled pleural catheter or by offering them pleurodesis? DR ROBERT J. CERFOLIO (Birmingham, AL): Excellent presentation and your last sentence is the key, because it is all about patient selection and it is all about the conversation with the
DR CERFOLIO: Because maybe they don’t know how it is going to change their management until you do it. DR WILLIAM A. COOK (North Andover, MA): There is a little area about the catheters that I think should be looked at, and that is that if the patient is going to have the tube for quite a while, they can get infection through these tunneled catheters. I have personally had 2; friends of mine at one of the major institutions in Boston have had 7. Now you have got a patient who has got empyema and cancer, and you are probably going to have to do something like a Clagett procedure, which is not really a very good outcome. So I just want you to know that that possibility exists in any patient who has got one of these tunneled catheters. DR J. ROBERT HEADRICK (Chattanooga, TN): What was the dosage of talc that you used, and do you think the dosage has any impact on outcome? DR HUNT: We performed 4 g talc poudrage in all patients. The optimal dose of talc has not been definitively determined, but has been looked at in various experimental and clinical settings. We think that 4 g to 5 g is an appropriate dose. If you use too much, you run the risk of systemic fibrosis and acute respiratory distress syndrome, and if you use too little you are not performing an adequate pleurodesis. DR GORDEN: If I could add a comment please. My name is Jed Gorden, I work with Dr Hunt, and I just wanted to add a comment. That was an excellent presentation thank you, Ben. With regard to the issue of empyema, raised by Dr Cook, I think that is a valid concern. In the largest series published, one by
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Suzuki from Memorial Sloan Kettering, and the other by Tremblay from the University of Calgary, the reported incidence of empyema was low. The Memorial Sloan-Kettering group reported 6 cases of empyema in 418 catheters placed, and the University of Calgary group reported 8 of 250 catheters placed. In our own review, we had 1 case of empyema among 59 catheters placed. While the consequence of an empyema in this setting are serious, the reported incidence remains low, and this concern should not be a barrier to tunneled pleural catheter placement.
DR HUNT: That’s a very good point. The downside of the tunneled pleural catheter obviously is management of the catheter after it has been placed. We have an interventional pulmonologist as part of our group and a center for pleural disease that has been established at Swedish Medical Center. So we do see most of the effusions and are able to take care of these patients long term. We have a dedicated nurse and a dedicated interventional pulmonologist who manage many of the catheter placements and all of the long-term follow-up.
DR STEPHEN C. YANG (Baltimore, MD): A very nice talk. I caution against a cookbook recipe like this, because, again, as Bob said, all the tumors are very different, especially for mesothelioma, which, again, you had a majority of. I tend to put PleurX catheters in so we can avoid an extrapleural pneumonectomy and just do a pleurectomy if the parietal pleura is not involved. Secondly, do you have total control of your pleural effusions? Because if you do not, how do you prevent your pulmonologist and your radiologist seeing the stain and saying, hey, we can do this, because we don’t need surgeons anymore. We are just going to be throwing these in left and right, which they do at our institution.
DR GORDEN: The last comment that I will make is that I think, Dr Yang, your point is excellent, and it is at the heart of whether a tunneled pleural catheter program will be successful. It is critical, and it is mentioned in the paper, that a PleurX catheter is not a procedure, it is a program, and as such it requires support from the nursing staff and from the medical staff. Patients must be evaluated and educated before catheter placement to insure that insurance issues are addressed, supplies are arranged, and a drainage and education infrastructure exists to support the patient and their caregiver. A tunneled pleural catheter should not add to the stress of patients and their caregivers in the palliative period of their illness.
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Thoracoscopic Talc Versus Tunneled Pleural Catheters for Palliation of Malignant Pleural Effusions Ben M. Hunt, MD, Alexander S. Farivar, MD, Eric Vallières, MD, Brian E. Louie, MD, Ralph W. Aye, MD, Eva E. Flores, LPN, and Jed A. Gorden, MD Division of Thoracic Surgery and Interventional Pulmonology, Center for Pleural Diseases, Swedish Cancer Institute, Swedish Medical Center, Seattle, Washington
Background. A malignant pleural effusion (MPE) is a late complication of malignancy that affects respiratory function and quality of life. A strategy for palliation of the symptoms caused by MPE should permanently control fluid accumulation, preclude any need for reintervention, and limit hospital length of stay (LOS). We compared video-assisted thorascopic (VATS) talc insufflation with placement of a tunneled pleural catheter (TPC) to assess which intervention better met these palliative goals. Methods. We conducted a retrospective chart review of consecutive MPE at a single institution from 2005 through June 2011. Primary a priori outcomes were reintervention in the ipsilateral hemithorax, postprocedure LOS, and overall LOS. Results. One hundred nine patients with MPE were identified. Fifty-nine patients (54%) had TPC placed, and 50 (46%) were treated with VATS talc. Patients who underwent TPC placement had significantly fewer rein-
terventions for recurrent ipsilateral effusions than patients treated with VATS talc (TPC 2% [1 of 59], talc 16% [8 of 50], p ⴝ 0.01). Patients treated with TPC had significantly shorter overall LOS (TPC LOS mean 7 days, mode 1 day; talc mean 8 day, mode 4 days, p ⴝ 0.006) and postprocedure LOS (TPC post-procedure LOS mean 3 days, mode 0 days; talc mean 6 days, mode 3 days, p < 0.001). Type of procedure was not associated with differences in complication rate (TPC 5% [3 of 59], talc 14% [7 of 50], p ⴝ 0.18), or in-hospital mortality (TPC 3% [2 of 59], talc 8% [4 of 50], p ⴝ 0.41). Conclusions. TPC placement was associated with a significantly reduced postprocedure and overall LOS compared with VATS talc. Also, TPC placement was associated with significantly fewer ipsilateral reinterventions. Placement of TPC should be considered for palliation of MPE-associated symptoms. (Ann Thorac Surg 2012;94:1053–9) © 2012 by The Society of Thoracic Surgeons
M
Several options exist for the treatment of MPE. The most common strategies are thoracentesis, pleurodesis, and placement of a tunneled pleural catheter (TPC). Thoracentesis is primarily a diagnostic procedure, and often also results in transient relief of symptoms [7, 8]. Pleurodesis may be attempted for recurrent symptomatic pleural effusions, either through a thoracostomy tube or during videoassisted thorascopy (VATS) [9]. Pleurodesis has a high success rate in selected patients (75% to 95%) [2, 9 –12], but it is an invasive procedure that requires hospitalization, has associated morbidity, and can be painful. Pleurodesis is not usually effective if the lung does not fully reexpand when the effusion is evacuated [7, 13–15]. The TPC can be used independent of the degree of lung expansion and can be managed by the patient or a designated caregiver [16 –18]. However, TPCs require ongoing drainage to manage the effusion and a support infrastructure to assist with drainage and supplies.
alignant pleural effusion (MPE) is an end-stage manifestation of many cancers [1]. The annual incidence of MPE in the United States has been estimated between 150,000 and 200,000 [1, 2]. Patients with MPE have a median survival of 4 to 6 months [3, 4]. Because MPE is associated with advanced malignancy, treatment is focused on palliating symptoms rather than cure. The ideal palliative procedure has a short length of stay (LOS), minimal future requirements for interaction with the medical system, good efficacy, and minimal postprocedure pain or complications [5, 6]. Accepted for publication Jan 11, 2012. Presented at the Fifty-eighth Annual Meeting of the Southern Thoracic Surgical Association, San Antonio, TX, Nov 9 –12, 2011. Address correspondence to Dr Gorden, Center for Pleural Diseases, Division of Interventional Pulmonology, Swedish Cancer Institute, Swedish Medical Center, 1101 Madison St, Ste 850, Seattle, WA 98104; e-mail: [email protected].
© 2012 by The Society of Thoracic Surgeons Published by Elsevier Inc
0003-4975/$36.00 doi:10.1016/j.athoracsur.2012.01.103
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Every option for the palliation of MPE-associated symptoms has potential disadvantages, and no one strategy is appropriate for every patient. The challenge is to select the appropriate management strategy for each individual patient, bearing in mind the goals of palliation. Because we currently employ several different strategies for the treatment of MPE, we performed a retrospective review of our management of MPE at a single institution to determine which strategy best achieved our palliative goals.
Patients and Methods A retrospective chart review was performed at a single institution from 2005 to June 2011. Patients were identified by a database query for International Classification of Diseases, Ninth Revision codes for VATS with pleurodesis (32650), TPC placement (32550), and chemical pleurodesis (32560). Because bedside pleurodesis by talc slurry is usually performed by residents without an attending present at our institution, bedside pleurodesis was not billable and was not identified by our query. Identified patient charts were reviewed to confirm the diagnosis of MPE and to abstract data on demographics, LOS, complications, inhospital mortality, cancer type, and repeat procedures on the ipsilateral hemithorax. A priori primary outcomes were overall LOS, LOS after the procedure, and ipsilateral reintervention. Secondary endpoints were complications, inhospital mortality, and hospital readmission for an ipsilateral effusion. Because many patients with MPE were hospitalized for other reasons before having a procedure to address the effusion, we analyzed both overall LOS and postprocedure LOS. The Institutional Review Board of Swedish Medical Center approved this study and waived the requirement for informed consent owing to the study’s retrospective nature. All patients in the VATS talc group had reexpansion of the lung at surgery. Four grams of aerosolized talc were insufflated into the chest under direct VATS observation. After VATS talc pleurodesis, a chest tube was placed, kept on 20 cm H2O suction for 48 hours, and then maintained on water seal until drainage dropped below 200 mL per day. Patients were normally discharged on the same day their chest tube was removed. Chest radiographs were obtained in the recovery room, daily while the chest tube was in place, and after chest tube removal. The TPCs used in this series were all PleurX catheters (CareFusion, San Diego, CA). The TPCs were either placed percutaneously using conscious sedation or at the time of VATS if VATS was required for another indication (such as pleural biopsies or a pericardial window). Additionally, if VATS talc was planned and the lung did not reexpand at the time of surgery, pleurodesis was not performed, and a TPC was placed instead. Before TPC placement, it was confirmed that the patient’s symptoms improved after removal of the effusion by thoracentesis. Potential candidates for TPC placement view an educational video and have an educational session conducted by a nurse or an interventional pulmonologist preoperatively. Care is taken to ensure that the patient’s insurance will cover the drainage supplies before insertion of the TPC. After TPC place-
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Table 1. Patient Demographics and Cancer Types Demographic Sex Female Male Mean age, years Cancer Type Lung Mesothelioma Breast Ovarian Gastrointestinal Other
TPC (n ⫽ 59)
Talc (n ⫽ 50)
p Value
38 (64%) 21 (36%)
27 (54%) 23 (46%)
0.36 0.36
66
66
0.95
TPC (n ⫽ 59)
Talc (n ⫽ 50)
Combined
27 (46%) 5 (8%) 10 (17%) 11 (19%) 2 (3%) 4 (7%)
15 (30%) 15 (30%) 5 (10%) 4 (8%) 6 (12%) 5 (10%)
42 (39%) 20 (18%) 15 (14%) 15 (14%) 8 (7%) 9 (8%)
TPC ⫽ tunneled pleural catheter.
ment, patients and their caregivers are taught to drain the TPC in a hands-on session. Catheters are then drained on a schedule that is individualized for each patient. The tests used for statistical comparisons were as follows: the t test for normally distributed continuous variables, the Mann-Whitney-Wilcoxon test for continuous variables with nonnormal distribution, Pearson’s 2 test with Yates’ continuity correction for discrete variables, and Fisher’s exact test for discrete variables with cell frequencies too low for the 2 test. All p values were two-tailed, and no adjustments were made for multiple comparisons. A p value less than 0.05 was considered statistically significant. All statistical analyses were performed using R software (available at: www.r-project.org).
Results One hundred nine consecutive patients with MPE were identified; TPCs were placed in 59 of 109 patients (54%), and 50 of 109 patients (46%) underwent VATS talc pleurodesis. Of the TPCs, 47 of 59 (80%) were placed using conscious sedation by the Seldinger technique, and 12 of 59 (20%) were placed during VATS. All talc pleurodeses in this series were done by VATS. One VATS talc case was converted to open to control bleeding from pleural biopsies (2% conversion rate). Patient demographics and cancer type (Table 1) were similar between the groups. With respect to primary endpoints, patients had shorter overall hospital LOS after TPC placement than VATS pleurodesis (Table 2). Postprocedure LOS was also significantly shorter after TPC placement (Table 2, Fig 1). Additionally, patients who underwent TPC placement had significantly fewer reinterventions for recurrent ipsilateral effusions (Table 2). Postprocedure complications were not significantly different between the two groups (Table 2). The following complications occurred: 1 patient who had a TPC placed by Seldinger technique had an empyema; 1 patient had respiratory failure and died after VATS for pleural biopsies and TPC placement; another patient had intraoperative bleeding after pleural biopsies as part of a VATS TPC placement;
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Table 2. Comparison Between Tunneled Pleural Catheter and Video-Assisted Thoracic Surgery Talc in Management of Malignant Pleural Effusion Variables LOS, days Mean Mode Postprocedure LOS, days Mean Mode Reintervention Complications Readmission for ipsilateral effusion In-hospital mortality LOS ⫽ length of stay;
TPC (n ⫽ 59)
Talc (n ⫽ 50)
p Value
7 1
8 4
0.006
3 0 1 (2%) 3 (5%) 7 (12%)
6 3 8 (16%) 7 (14%) 6 (12%)
⬍ 0.0001
2 (3%)
4 (8%)
0.41
0.01 0.18 0.78
TPC ⫽ tunneled pleural catheter.
and the following complications occurred after VATS Talc, each in 1 patient: acute respiratory distress syndrome, exacerbation of hepatic encephalopathy, hypoxia requiring home oxygen, intraoperative bleeding after pleural biopsies, empyema, wound dehiscence, and atrial fibrillation. There was no difference in the rate of hospital readmission for ipsilateral pleural effusion (Table 2). The type of procedure was not associated with a significant difference in in-hospital mortality (Table 2).
Comment Malignant pleural effusion significantly affects patient quality of life [1, 2]. Currently, several options exist for the treatment of MPE (Table 3). Most published guidelines for management of MPE begin with a recommendation for thoracentesis, which provides diagnostic and therapeutic value [1, 7, 13, 14]. Thoracentesis evaluates lung entrapment and whether symptoms are relieved by draining the effusion. Both are critical branch points when evaluating future palliative options [7]. If the MPE recurs, a definitive palliative strategy should be considered. Chemical pleurodesis is the traditional pro-
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Table 3. Strategies for Managing Malignant Pleural Effusion Observation Palliation with oxygen and narcotics Serial thoracentesis Tunneled pleural catheter Bedside pleurodesis through a chest tube Pleurodesis at thoracoscopy
cedure used to treat recurrent MPE [19, 20]. Pleurodesis attempts to achieve fusion of the visceral and parietal pleura and requires lung reexpansion [13]. The disadvantages of pleurodesis relate to pain and the requirement for hospitalization [2]. The Cancer and Leukemia Group B (CALGB) 9334 trial did not find a difference in overall pleurodesis rate between VATS talc and talc slurry by chest tube, but a post-hoc subgroup analysis favored VATS in patients with near-complete lung reexpansion and in patients with breast and lung cancers [9]. The higher pleurodesis rate after VATS was also seen in a Cochrane review that predates the CALGB trial [21]. Many agents have been used to fuse the pleural space, including talc, povidoneiodine, doxycycline, dextrose, and other sclerosants [21]. Talc was clearly favored over other sclerosants in a Cochrane review [21]. Pulmonary complications with talc pleurodesis have been reported including the development of acute respiratory distress syndrome [22, 23]. Various approaches have been tried to mitigate the morbidity of pleurodesis [24, 25], but it still requires a hospital stay, is a painful procedure, and is not useful unless the lung fully reexpands when the effusion is drained. The TPC was approved by the Food and Drug Administration for managing recurrent MPE in 1997 [26], and TPCs are increasingly used for this indication. They are the preferred palliative method for patients with lung entrapment [16 –18]. The minimally invasive nature of the TPC allows it to be placed for palliation in a wide range of patients with varying performance status, and a TPC does not require lung expansion to achieve palliation. The TPC can be placed in the outpatient ambulatory setting [27, 28]. Good symptom control has been reported in large series of patients treated with TPCs [27], and our series confirms that Fig 1. Postprocedure length of stay (LOS) after video-assisted thorascopic (VATS) talc (white bars) and tunneled pleural catheter (TPC) placement (black bars).
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Fig 2. Proposed management strategy for management of pleural effusions in patients with cancer. (CXR ⫽ chest radiograph; TPC ⫽ tunneled pleural catheter.)
TPCs can be placed with acceptable rates of morbidity and in-hospital mortality. Although TPCs can achieve pleurodesis in as many as 72% of selected patients [29], this population cannot be identified a priori, and most patients will require lifelong serial drainage [18, 27, 30]. Like any indwelling device, they carry a risk of infection; the incidence of empyema with TPCs has been reported from 2% to 12% [5, 18, 27, 31] and was 2% in this study. Lastly, and importantly, the implantation of a TPC must be considered a program and not simply a procedure. A clinical infrastructure must be created to support patients and their caregivers, who will require preprocedure counseling, insurance assistance, and postprocedure education and support. For a frail, end-stage population, we conclude that TPCs afforded better palliation than VATS talc by our criteria, because patients had shorter overall hospitalizations and shorter postprocedure length of stay. The TPC resulted in fewer ipsilateral reinterventions when compared with VATS talc, thus requiring fewer interactions with the health care system. These findings suggest TPC placement may be more optimal than pleurodesis for palliation in patients who have a poor prognosis and a short expected lifespan.
It remains unclear whether pleurodesis or TPC is a better option for palliation of symptoms in patients who do not have lung entrapment, have a good performance status, and have a relatively long life expectancy. Cost analysis studies have favored pleurodesis for patients with longer life expectancy [32, 33]. The TPC was found to have a similar success rate with a shorter hospital stay when compared with doxycycline pleurodesis [16]. The CALGB 30102 trial randomly allocated 58 patients with MPE to talc slurry pleurodesis or TPC, and TPC had higher technical success, better dyspnea scores, and performed better on the composite endpoint of death or effusion recurrence, but the trial was stopped early owing to insufficient accrual [34]. Thus far, VATS talc pleurodesis has not been compared with TPC in a prospective, randomized setting. Our current algorithm for management of MPE is presented in Figure 2. This case series is limited by its retrospective nature. We did not capture data on symptoms, cost, comorbidities, or functional status. An additional inherent limitation is patient selection bias. Although this series is neither controlled nor randomized, it provides evidence that patients with MPE treated with TPC needed fewer reinterventions
and were out of the hospital sooner than the patients who underwent VATS talc pleurodesis. Any treatment strategy for MPE must be evaluated with respect to palliative goals: limiting hospitalizations, procedures, and pain while providing durable symptom control. In patients with poor performance status, palliation can be achieved with the low-risk outpatient placement of a TPC. For patients with longer life expectancy and better performance status, it remains an individual decision between the provider and the educated patient whether to perform pleurodesis or place a TPC. Further prospective studies are required to validate the decisionmaking algorithm presented here. The authors would like to acknowledge the support of the Ryan Hill Foundation.
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16.
17. 18.
19. 20. 21. 22.
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DISCUSSION DR TODD L. DEMMY (Buffalo, NY): Nice presentation, Ben. Thank you for the manuscript. The optimal therapy for malignant pleural effusions is controversial, and it is surprising that it is an understudied problem despite how commonplace it is for
thoracic surgeons. Study accrual can be challenging for these patients who are distressed by their dyspnea and have limited life expectancy despite this palliative intervention. In CALGB 30102, 57 patients were randomized between a primarily outpa-
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tient procedure, that is, the PleurX or the tunneled catheter, versus an inpatient talc slurry, and this study was closed early for slow accrual. But like your study, we saw that there was better effusion control at 1 month with the tunneled catheter, and we found that the symptom control correlated well with persistence of lung expansion. This leads to question number one. The tunneled catheter was intended to be an outpatient procedure and yet about 60% of your patients had a postoperative stay of 1 day in the hospital. Please comment further on your rationale to use this as an inpatient therapy and tell us if any patients had outpatient catheter placement. In a similar vein, also comment on why no patients had talc delivered by chest tube slurry given its equivalence to VATS talc in CALGB 9334. And lastly, question number two relates to the algorithm that you just showed that recommends either talc or a tunneled catheter for the full expanders. Since your pooled survival analysis favors talc is biased by the greater number of mesothelioma patients in this group and the fewer number of trapped lungs in this cohort, have you tried to use case matching, propensity scores, or something similar to that to compare those outcomes? In particular, have you analyzed just the outcomes of the group that had full expansion in this study?
patient. Some people don’t want a tube hanging out of their side for 3 months, and so it is an easy decision. But I think the one thing you have underplayed is that box about the pleural biopsy. I can’t tell you how now genomics has changed our practice over the past few years. I have been sending our tumors for genetic testing for 4 or 5 years now, but the oncologists were not interested—now everyone wants to see “the tumor biology”—like it is some new concept. We are doing more mediastinoscopies than EBUS and EUS, because we want to get EML ALK4s, we want to get EGFR and PTEN, and so forth. It is the same thing here. I can’t tell you how many patients we have who have been told they have metastatic lung cancer by cytology, but you put a scope in and you biopsy it, and they are ER/PR positive for metastatic breast cancer—real information that will change their therapy. So I think when you do your study, you need to include the fact that with a VATS and a pleural biopsy you get a lot more information and you put patients on an oral or more gentle and efficacious chemotherapy. Although they have a short duration of life, oral chemotherapy may improve their quality of life. So, do you have any comments on how it affected their care, not just with securing the diagnosis but also in getting genomics and guided therapy?
DR HUNT: Thanks for your comments and questions. In regard to the 60% of patients who had a 1-day hospital stay, that is strictly an issue of nomenclature. Those patients were treated on an outpatient basis, and we counted the 1 day as the day the procedure was performed. So that’s a little bit confusing. But that 1-day stay is the day that the procedure was performed. Then you asked about talc slurry versus VATS talc. We do perform talc slurry in some patients at our institution; however, we did not include those patients in this analysis. It was difficult to pull those charts retrospectively based on simply a codebased query. But since a lot of the patients we see have either lung or breast cancer, which was a subset that did better with VATS talc than talc slurry through chest tube in the CALGB trial you performed, we do tend to favor VATS talc in those patients who are able to undergo the procedure.
DR HUNT: Thanks for the comment. We agree completely that the goal in these patients is to palliate their symptoms and then limit their interaction with the medical system as much as possible. So in those cases when pleural biopsies would definitively change management, we favored pleural biopsy, but if the oncologist wasn’t going to change management based on the results of the pleural biopsy, then we usually did not perform VATS because of its associated complications.
DR DEMMY: The other question was regarding patients whose lungs can expand fully— did you look at that group alone? This is because your survival curves are biased by the larger proportion of mesothelioma patients for the talc and the trapped lungs in the tunneled catheter groups. DR HUNT: We did not look at those patients who had complete reexpansion of their lungs versus those patients who did not have complete reexpansion. We intended to go after those data, but from the operation notes and review of the hospital records, we couldn’t tease out which patients had complete reexpansion of their lungs. All these are very good points; they are clear limitations of a retrospective study, and so we together with CALGB would like to perform a prospective study comparing VATS talc with tunneled pleural catheters, because we think this is an important question that faces a lot of thoracic surgeons. In these patients with good performance status with a long life expectancy with a lot of options for treating their cancer, are patients better served by placing a tunneled pleural catheter or by offering them pleurodesis? DR ROBERT J. CERFOLIO (Birmingham, AL): Excellent presentation and your last sentence is the key, because it is all about patient selection and it is all about the conversation with the
DR CERFOLIO: Because maybe they don’t know how it is going to change their management until you do it. DR WILLIAM A. COOK (North Andover, MA): There is a little area about the catheters that I think should be looked at, and that is that if the patient is going to have the tube for quite a while, they can get infection through these tunneled catheters. I have personally had 2; friends of mine at one of the major institutions in Boston have had 7. Now you have got a patient who has got empyema and cancer, and you are probably going to have to do something like a Clagett procedure, which is not really a very good outcome. So I just want you to know that that possibility exists in any patient who has got one of these tunneled catheters. DR J. ROBERT HEADRICK (Chattanooga, TN): What was the dosage of talc that you used, and do you think the dosage has any impact on outcome? DR HUNT: We performed 4 g talc poudrage in all patients. The optimal dose of talc has not been definitively determined, but has been looked at in various experimental and clinical settings. We think that 4 g to 5 g is an appropriate dose. If you use too much, you run the risk of systemic fibrosis and acute respiratory distress syndrome, and if you use too little you are not performing an adequate pleurodesis. DR GORDEN: If I could add a comment please. My name is Jed Gorden, I work with Dr Hunt, and I just wanted to add a comment. That was an excellent presentation thank you, Ben. With regard to the issue of empyema, raised by Dr Cook, I think that is a valid concern. In the largest series published, one by
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Suzuki from Memorial Sloan Kettering, and the other by Tremblay from the University of Calgary, the reported incidence of empyema was low. The Memorial Sloan-Kettering group reported 6 cases of empyema in 418 catheters placed, and the University of Calgary group reported 8 of 250 catheters placed. In our own review, we had 1 case of empyema among 59 catheters placed. While the consequence of an empyema in this setting are serious, the reported incidence remains low, and this concern should not be a barrier to tunneled pleural catheter placement.
DR HUNT: That’s a very good point. The downside of the tunneled pleural catheter obviously is management of the catheter after it has been placed. We have an interventional pulmonologist as part of our group and a center for pleural disease that has been established at Swedish Medical Center. So we do see most of the effusions and are able to take care of these patients long term. We have a dedicated nurse and a dedicated interventional pulmonologist who manage many of the catheter placements and all of the long-term follow-up.
DR STEPHEN C. YANG (Baltimore, MD): A very nice talk. I caution against a cookbook recipe like this, because, again, as Bob said, all the tumors are very different, especially for mesothelioma, which, again, you had a majority of. I tend to put PleurX catheters in so we can avoid an extrapleural pneumonectomy and just do a pleurectomy if the parietal pleura is not involved. Secondly, do you have total control of your pleural effusions? Because if you do not, how do you prevent your pulmonologist and your radiologist seeing the stain and saying, hey, we can do this, because we don’t need surgeons anymore. We are just going to be throwing these in left and right, which they do at our institution.
DR GORDEN: The last comment that I will make is that I think, Dr Yang, your point is excellent, and it is at the heart of whether a tunneled pleural catheter program will be successful. It is critical, and it is mentioned in the paper, that a PleurX catheter is not a procedure, it is a program, and as such it requires support from the nursing staff and from the medical staff. Patients must be evaluated and educated before catheter placement to insure that insurance issues are addressed, supplies are arranged, and a drainage and education infrastructure exists to support the patient and their caregiver. A tunneled pleural catheter should not add to the stress of patients and their caregivers in the palliative period of their illness.
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