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* From the National Cancer Institute of Canada Clinical Trials Group (Dr. Parulekar), Queen’s University, Kingston ON; the Department of Radiology (Drs. Di Primio, Matzinger, and Dennie), University of Ottawa, Ottawa ON; the Department of Internal Medicine, Section of Hematology/Oncology (Dr. Bociek), University of Nebraska Medical Centre, Omaha, NE.
Correspondence to: Wendy Parulekar, MD, National Cancer Institute of Canada Clinical Trials Group, Queens University, 82 Barrie St, Kingston, Ontario K7L 3N6, Canada; e-mail: wparulekar{at}ctg.queensu.ca
Abstract
Study objective: To evaluate the efficacy of small-bore (12 French vanSonnenberg) catheters compared with standard large-bore chest tubes in the drainage and sclerotherapy of malignant pleural effusions.
Design: Retrospective review.
Setting: An academic tertiary care hospital.
Patients: Adult patients with documented neoplasms and malignant pleural effusions, treated between 1986 and 1995.
Intervention: All patients included in the study underwent drainage of malignant pleural effusions either by large-bore chest tube or by ultrasound-guided small-bore catheter. After drainage, pleurodesis was performed.
Results: Outcome as defined by recurrence of effusion was determined by blinded examination of all postpleurodesis chest radiographs. We identified 58 cases of malignant pleural effusion in which small-bore catheters were used and 44 in which large-bore chest tubes were used. The majority of patients had breast (n = 56, 55%) or lung cancer (n = 29, 28%). The median age was 65 years. Fifty-nine patients were actively being treated with chemotherapy at the time of pleurodesis. The following sclerosing agents were used: talc, 27 (26%); tetracycline, 72 (70%); bleomycin, 2 (2%); and interferon, 1 (1%). Actuarial probabilities of recurrence at 6 weeks and 4 months were 45% and 53% for the small tubes vs 45% and 51% for the large tubes. Univariate and multivariate analyses failed to demonstrate that tube size had any influence on the rate of recurrence.
Conclusions: We were unable to detect any major differences in outcomes with the use of either size of chest tube. Our study suggests that small-bore catheters may be effective in the treatment of malignant pleural effusions and deserve further evaluation in prospectively designed trials.
Key Words: chest tubes • complications • indwelling catheters • malignant pleural effusion • pleurodesis • recurrence
Malignant pleural effusions occur commonly in cancer patients, especially in those with tumors of the lung, breast, and lymphoma.1 Although most of these patients have advanced disease, with a poor prognosis, some patients with chemosensitive tumors such as breast cancer may be associated with a relatively prolonged survival.2 In a significant number of patients, specific treatments of the effusions are often justifiable in an attempt to palliate symptoms such as dyspnea, orthopnea, cough, and pleuritic pain. Systemic therapy, alone or in combination with local therapy, is a reasonable treatment option in patients with chemosensitive tumors (ie, small cell lung cancer, breast cancer, lymphoma). However, in many instances, systemic chemotherapy will not constitute an effective means of treating a malignant effusion, and local therapy is likely to be of greater benefit to the patient. Local measures include thoracentesis (which may be repeated as necessary) and tube thoracostomy, although neither affords a high probability of long-term control of the effusion.1 3 4 The high rate of reaccumulation of fluid after simple drainage has provided the rationale behind the use of sclerosing agents to attempt to obliterate the pleural space and to reduce the probability of recurrence.
Most of the existing literature on treatment has focused on the comparative efficacy of specific sclerosing agents such as talc, tetracycline, and bleomycin.3 4 5 6 7 8 9 10 11 12 In addition, there has also been interest in the use of less invasive techniques of fluid drainage and sclerosis, including the use of small-bore catheters in lieu of larger, standard bore chest tubes. The use of small-bore catheters in the treatment of fluid collection in the pleural space has been reported in the radiology literature sporadically for almost 20 years. The therapeutic indications for catheter placement have included treatment of empyema, pneumothorax, and drainage of pleural effusions, with or without sclerotherapy. The experience to date suggests that the use of small-bore catheters is effective, safe, and well-tolerated.13 14 15 16 17 18 19 20 21 22 23 24 25 26 In addition, the use of catheter placement guided by ultrasound offers these theoretical advantages: 1) ensuring that the tube is placed just above the diaphragm to maximize drainage of the effusion; and 2) assessment of the presence of loculation(s) and optimizing catheter placement and potential fluid drainage based on the location of these. However, the question regarding efficacy of these catheters, compared with conventional large-bore chest tubes, remains unanswered.
The purpose of our study was to evaluate the efficacy of small-bore (12 French vanSonnenberg) catheters compared with standard large-bore chest tubes in the drainage and sclerotherapy of malignant pleural effusions.
Materials and Methods
We conducted a retrospective review of patients treated at a tertiary hospital between 1986 and 1995. This time period allowed us to maximize the size of the study cohorts, and it corresponded to a period when there were no dramatic changes in the systemic treatment of advanced solid tumors that would have significantly influenced the outcome variables chosen for this study. The potential study population was determined by reviewing all charts, which indicated discharge diagnostic codes for pleural effusion, chest tube insertion, pleurodesis, or sclerotherapy. This identified patients admitted to the thoracic surgery, oncology, and respirology services. Individual patient charts were then reviewed, and only symptomatic patients with confirmed malignancy, no clear nonmalignant etiology for the effusion (eg, congestive heart failure), and adequate follow-up chest radiographs were included in the final study population.
Information collected for each patient included demographics, date of initial diagnosis, type of malignancy, treatment status (ie, prior or ongoing chemotherapy), and the presence of other concurrent illness predisposing to a pleural effusion. Biochemical and cytological characteristics of the pleural effusion were recorded when available. For all patients, recurrences were determined by blinded examination of all postpleurodesis radiographs by two independent chest radiologists. Recurrence was defined as re-accumulation of pleural fluid greater than that seen on the baseline post-pleurodesis chest radiograph. When lack of agreement occurred, a consensus opinion was obtained between the two radiologists. Follow-up time was calculated from the date of pleurodesis to the date of last radiograph or recurrence of the effusion. The actuarial method was used to compare time to recurrence between groups. Patients without evidence of recurrence on the last known chest radiograph were censored at that point in time.
Statistical Analysis
Results were analyzed as follows: time-dependent data (time to
failure of pleurodesis, survival data) was generated using the
Kaplan-Meier product limit method.27
All time dependent
outcomes were calculated from the date of tube insertion. Patient data
were censored where the outcome of interest had not yet occurred at
last follow-up. Univariate analyses for comparing baseline
characteristics of the two groups were performed using
2 analysis. Univariate analyses for
time-dependent events were performed using a univariate Cox
proportional hazards model.28
Multivariate analysis using
stepwise regression analysis and the Cox proportional hazards model was
performed to identify factors independently associated with time to
event outcomes. Statistical software used included BMDP for
Windows (descriptive statistics, 2 analysis),
BMDP Classic (BMDP Statistical Software; Cork, Ireland), and
Graphpad Prism (generation of survival curves, log-rank tests)
[Graphpad Software; San Diego, CA].
Results
Of 159 cases of pleural effusion initially identified, 57 cases were excluded from analysis for the following reasons: empyema, 14; pleural effusion related to alcoholic cirrhosis, 1; pleurodesis not performed, 30; early death unrelated to tube insertion and prior to pleurodesis, 3; lack of follow-up chest radiographs, 8; lost to follow-up, 1. The final study group was formed from the remaining 102 cases. The median age was 65 (range, 44 to 92) years. Fifty-eight patients were treated with small-bore catheters, and 44 patients received conventional large-bore chest tubes. The most common diagnoses were breast cancer (56 patients, 55%) and non-small cell lung cancer (28 patients, 27%). Sixty-seven patients (66%) had received prior systemic therapy. Fifty-nine patients (58%) were receiving ongoing chemotherapy. Seven (7%) had other concurrent nonmalignant disease that may have predisposed to a pleural effusion. Cytologic evaluation was performed on 70 patients and was positive in 56 patients (80%). Table 1 reveals the baseline characteristics of the two groups. After adjusting for the statistical effect of multiple testing, no significant differences were found between the groups with respect to these characteristics.
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2
= 0.91, degrees of freedom
[df] = 3, p = 0.82). Talc was administered in the form
of a slurry to patients treated with small-bore catheters and via
insufflation to patients treated with large-bore chest tubes. All
patients included in this analysis had pleurodesis performed only once
on the side (left or right) in which response was measured.
Complications of Therapy
We examined the complication rate of patients in each group with
emphasis on the following: (1) the development of intercurrent
infection during the time that the tube was in place, (2) the incidence
of radiographically evident pneumothorax, and (3) the probability of
death during the procedure. In total, 11 patients developed infection;
6 (14%) in the large tube group and 5 (9%) in the small tube group.
This difference was not statistically different
(2 = 0.65, df = 1, p = 0.42).
Radiographically evident pneumothoraces were seen in 28 patients—16
(36%) patients from the large-bore group vs 12 patients (21%) of the
small-bore group. This difference was of borderline significance
(2 = 3.08, df = 1, p = 0.08).
There was no difference in the probability of death during the time
that the tube was in place. Three patients (7%) in the large tube
group died, compared with 4 (7%) in the small tube group.
Differences in Time of the Procedure
We examined various timelines associated with the procedures.
These included time from tube insertion to pleurodesis, average total
duration of tube placement, time to discharge after removal of the
tube, and the total length of stay. These results are summarized in
Table 2 . Although there were trends suggesting shorter times to pleurodesis for
patients with large tubes and shorter times to discharge and total
length of stay for patients with the smaller tubes, none of these
reached statistical significance after adjusting for multiple testing.
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Duration of Response
Time to recurrence was assessed in a blinded manner by two
independent radiologists. Lack of agreement occurred in < 10 cases
and was easily resolved by consensus opinion.
The actuarial probabilities of recurrence at 6 weeks and at 4 months were 45% and 53% for the small-bore catheters, compared with 41% and 51% for the large-bore chest tubes. Although as a single point on the curve the median time to recurrence was longer for the large-tube group when compared to the small-catheter group (19 weeks vs 7 weeks, respectively), the overall probability of recurrence over time was not different between the two groups (Fig 1 , p = 0.43 by log-rank).
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We also reviewed outcomes in the subset of patients (n = 70) for whom information on cytology was available. This analysis revealed that the presence of malignant cells in the effusion was a highly significant independent predictor of a shorter time to recurrence (Fig 2 , RR = 12.2, 95% CI = 10.2 to 14.3, p = 0.007) as was gender (for men, RR = 5.3, 95% CI = 4.2 to 6.4, p = 0.02), and perhaps the use of current systemic therapy (RR = 1.8, 95% CI = 0.9 to 2.7, p = 0.06). However, even in this subset of patients, multivariate analysis revealed that tube size was not significant (p = 0.27).
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In the vast majority of patients, the treatment of malignant pleural effusions is palliative and, therefore, should be associated with a low morbidity and mortality rate. Recent interest in the use of small-bore catheters for effusion drainage and sclerotherapy is based on the premise that it may be less invasive as a procedure and thus better tolerated by patients compared to standard large-bore chest tubes, with no compromise in efficacy. The literature examining the use of catheters for management of diseases of the pleural space is encouraging.
One case series examined the efficacy and complication rate of 133 percutaneous pigtail catheters placed in 91 children in a pediatric ICU.29 The majority of patients had congenital heart disease. Eighty-five percent of the catheters were placed for pleural effusion drainage, the remainder for treatment of pneumothorax. The catheter was found to be highly effective for drainage of serous and chylous effusions, less so for hemothorax or empyema. Five percent of catheter placements were associated with serious complications (hemothorax, pnuemothorax, and hepatic perforation). Complications of catheter use occurred in 20% of patients and included failure to drain, dislodgement, kinking, empyema, and disconnection.
Other studies demonstrated the efficacy and safety of small-bore catheters in the adult population for treatment of pneumothorax and uncomplicated pleural effusion due to various conditions.21 30 31 Gammie et al31 retrospectively reviewed the outcome of 109 consecutive pigtail catheters placed at the bedside (ie, without radiographic guidance). No complications of placement were seen, despite the fact that 24% of patients had laboratory evidence of coagulopathy. Another study demonstrated that the use of a small indwelling pleural catheter was more cost-effective when used in place of a closed tube thoracostomy for drainage of large-volume pleural effusions.30
Others have evaluated the use of small-bore percutaneous catheters in combination with sclerotherapy (using tetracycline or bleomycin). Walsh et al32 treated 15 consecutive patients with disseminated disease and symptomatic pleural effusion using a 9F catheter. Eleven of 12 patients who lived for > 4 weeks had objective clinical responses. Five patients had complete roentgenographic responses; another 5 had only slight reaccumulation or thickening. Complications were minimal. Spontaneously resolving, small, apical pneumothoraces developed in 4 of the 15 patients. One patient experienced re-expansion pulmonary edema before pleurodesis. Efficacy of this method was confirmed in two other studies, both involving 21 patients.23 33 Each study demonstrated a success rate of 71% with minimal treatment-related morbidity.
The largest case series was reported by Seaton et al.24 Forty-seven patients underwent small tube drainage and doxycycline sclerotherapy. Twenty-one patients had radiographic follow-up at 30 days and formed the study group. Seventeen patients (81%) had a complete response and three patients (14%) had a partial response based on the 30-day chest radiograph. Again, the complication rate was low and consisted of symptoms such as pain and fever.
The incidence and significance of pneumothorax after small-bore catheter placement for malignant pleural effusions was examined by Chang et al25 in a retrospective review of 88 patients treated over a 2-year period. Twenty-seven patients with 28 catheters developed a pneumothorax. Resolution occurred in 22 patients; in the remaining 6, the pneumothorax was stable. No complications such as tension pneumothorax, or respiratory distress were reported.
Parker et al22 compared the efficacy of small-bore catheter drainage and sclerosis to traditional drainage with standard chest tube in a retrospective single institution review involving 20 patients with a total of 24 malignant pleural effusions. Treatment consisted of drainage with a pigtail catheter or standard chest tube followed by tetracycline sclerotherapy. Success was determined by the status of the pleural effusion at 30 days. Eight of 13 effusions were adequately treated using the small-bore catheter, compared with 4 of 11 effusions treated with the standard chest tube. The authors concluded that the pigtail catheter drainage and sclerosis was at least as successful as the more traditional drainage with standard chest tube.
The results of our study support this conclusion. We were unable to detect a significant difference in recurrence rates between small-bore catheters compared with large-bore chest tubes in cancer patients with symptomatic effusions. Using the actuarial method, no significant difference in time to recurrence was found between the two groups. To control for potential confounding factors (eg, primary diagnosis, prior or concurrent therapy, etc.), univariate and multivariate analyses were performed. Again, tube size remained nonsignificant. It is worth noting that male gender (RR = 2.5) and previous systemic therapy (RR = 1.8) were found to be significant predictors of relapse. The latter result may be explained by the fact that prior therapy may be a marker for more advanced or aggressive disease. For those patients who underwent cytologic testing, a positive result was found to be highly significant as a predictor of failure (RR = 5.3). The use of concurrent systemic therapy was of borderline significance.
As expected, the complication rates associated with the chest tube insertions and sclerotherapy were low. There were no significant differences in the rates of infection or radiographically detected pneumothoraces. Although the latter achieved borderline statistical significance (p = 0.08), the clinical significance remains doubtful. As anticipated, there was no difference in survival between the two groups. In fact, the similar median survival of both groups (4.4 months and 3.2 months for the large-bore and small-bore tubes, respectively) suggests that the groups were comparable with respect to disease-related prognosis.
The issue of relative efficacy and safety of small-bore catheters compared to chest tubes is unresolved. Interpretation of the current literature is problematic due to various methodologic issues, the principal issue being a lack of prospective randomized trials comparing the two methods of treatment. Other criticisms include small patient numbers, heterogeneous patient populations, lack of documentation of coexisting heart or lung disease (when defining subjective response), failure to define the criteria for diagnosis of malignant pleural effusion, and a lack of standardized follow-up and definition(s) of response.
We were able to address some but not all of these issues. Cytologic confirmation of malignant pleural effusion was sought in all cases during chart review, although positive results were documented in only 55% of the study population. To minimize this problem, careful chart examination was performed to exclude other causes of pleural effusion such as cardiac or renal failure. In accordance with others,34 we defined response in terms of recurrence rate of the effusion compared to a baseline postpleurodesis chest radiograph rather than the traditional solid tumor response system (ie, complete and partial responses). Another strength of our study was the duration of follow-up. Similar to Morrison et al,33 we collected clinical and radiologic follow-up to the time of last visit or death rather than using an arbitrary time period such as 4 weeks. In addition, blinded evaluation of all chest radiographs was performed by two independent radiologists in an attempt to minimize bias in assessing response. The major limitation of our study was the retrospective design, which might have amplified the effects of bias and confounding. We were unable to derive information from the chart, which may have influenced the outcome of the intervention such as performance status and prior mediastinal irradiation. Issues of bias with respect to choice of tube size are diminished somewhat by the fact that the majority of large tubes were inserted during the early part of the study (ie, from 1986 to 1992), and the majority of small tubes were inserted during a later period of the study (ie, from 1993 to 1995). This suggests that tube selection was influenced mainly by a time-dependent bias, although other factors likely influenced the choice. Another limitation of the study is the small sample size, which would likely have limited the power to detect anything other than a moderate or large difference in efficacy rates (ie, we could have missed a small difference in effect). Finally, we were unable to derive information on what we consider to be two important endpoints—cost and quality of life. These issues are especially important in light of evidence demonstrating that drainage and sclerotherapy of malignant pleural effusions can be done safely and effectively in the ambulatory setting.35
Conclusion
Ultrasound-guided placement of small-bore catheters appears to be a safe and promising tool in the treatment of malignant pleural effusions. Relative efficacy compared with the traditional large-bore chest tube is unknown and deserves further investigation, preferably in the context of a randomized, prospective trial. Associated morbidity rates and costs also warrant further analysis.
Footnotes
Abbreviations: CI=confidence interval; df = degrees of freedom; RR = relative risk
Study performed at the University of Ottawa, Ontario, Canada. No financial support was requested or used in the generation of these data or this publication.
Received for publication June 16, 2000. Accepted for publication February 1, 2001.
References
This article has been cited by other articles:
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  A. R. Haas, D. H. Sterman, and A. I. Musani Malignant Pleural Effusions: Management Options With Consideration of Coding, Billing, and a Decision Approach Chest, September 1, 2007; 132(3): 1036 - 1041. [Abstract] [Full Text] [PDF]
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 C. Tan, A. Sedrakyan, J. Browne, S. Swift, and T. Treasure The evidence on the effectiveness of management for malignant pleural effusion: a systematic review. Eur. J. Cardiothorac. Surg., May 1, 2006; 29(5): 829 - 838. [Abstract] [Full Text] [PDF]
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Y. Aelony and W. Parulekar Dry Talc Pleurodesis Via Chest Tube Chest, January 1, 2003; 123(1): 308 - 308. [Full Text] [PDF]
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G. Cardillo, F. Facciolo, L. Carbone, M. Regal, F. Corzani, A. Ricci, M. Di Martino, and M. Martelli Long-term follow-up of video-assisted talc pleurodesis in malignant recurrent pleural effusions Eur. J. Cardiothorac. Surg., February 1, 2002; 21(2): 302 - 306. [Abstract] [Full Text] [PDF]
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