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1 Department of Radiology, Duke University Medical Center, Box 3808, Durham, NC
27710.
2 Department of Radiology, The University of Texas M. D. Anderson Cancer Center,
Box 57, Houston, TX 77030.
3 Department of Biostatistics and Bioinformatics, Duke University Medical
Center, Durham, NC 27710.
Received September 6, 2001;
accepted after revision January 2, 2002.
Address correspondence to E. M. Marom.
Abstract
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MATERIALS AND METHODS. Twenty-five patients (mean age, 63 years) with metastatic gynecologic malignancies who had 26 symptomatic effusions treated at our institution over a 4-year period with imaging-guided catheter drainage and talc sclerotherapy were included in this study. Response to treatment was assessed by comparing pre-, immediate post-, and 30-day postsclerotherapy chest radiographs. Response to the treatment was graded as complete (no reaccumulation), partial (accumulation above immediate post- but below presclerotherapy level), or no response (reaccumulation to or above the presclerotherapy level). The presence of ascites on CT (n = 23), sonography (n = 1), direct intraoperative visualization (n = 1), or at physical examination (n = 1) was also noted.
RESULTS. Of the 25 patients, 13 patients with 14 treated malignant effusions survived at least 30 days after sclerotherapy and formed the final study group. The remaining patients either died (n = 11) or were lost to follow-up (n = 1). At 30 days, 12 of the 14 treated effusions showed complete responses and one showed a partial response. The overall response rate was 86%. Abdominal ascites was present at the time of treatment in 11 patients (79%) and did not affect the success rate (p > 0.999).
CONCLUSION. Imaging-guided catheter drainage and talc sclerotherapy are an effective treatment for symptomatic pleural effusions in patients with metastatic gynecologic malignancies. Ascites does not adversely affect the response to pleurodesis.
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Patients with gynecologic malignancies frequently develop peritoneal metastases and ascites. Because peritoneal fluid readily crosses the diaphragm, negative pressure in the pleural cavity may draw ascitic fluid into the pleural space; a similar phenomenon is seen in patients with hepatic hydrothorax [2,3,4,5,6]. Thus, patients with gynecologic malignancies and ascites may develop rapid accumulation of pleural fluid during and after drainage. Reaccumulation of ascitic fluid in the pleural space and dilution of the sclerosant may thus reduce the effectiveness of chemical pleurodesis. One might speculate, therefore, that tube thoracostomy and chemical pleurodesis might be less effective in patients with metastatic gynecologic malignancies than in patients with other metastatic malignancies.
The purpose of our study was to report our experience with imaging-guided catheter drainage and talc sclerotherapy of patients with gynecologic malignancies and symptomatic pleural effusions to determine the success rate of that treatment and to assess the affect of ascites on the likelihood of treatment success or failure.
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Upright posteroanterior and lateral chest radiographs (n = 26, 100%) and thoracic CT scans (n = 23, 88%) obtained before chest tube placement were reviewed for the size and location (left, right, or bilateral) of the pleural effusion. In patients with bilateral effusions, the larger effusion was always treated. The size of the pleural effusion was defined as small (less than one quarter of the hemithorax on an upright radiograph), moderate (between one quarter and one half of the hemithorax on an upright radiograph) or large (more than one half of the hemithorax on an upright radiograph). The presence or absence of ascites on CT (n = 23), sonography (n = 1), direct intraoperative visualization (n = 1), or at physical examination (n = 1) performed within 1 month of treatment was also noted. Ascites was graded as small when it was seen only in the pelvis with the patient in the supine position and large when it was also seen in the upper abdomen or was clearly evident at physical examination. Clinical records were reviewed noting total volume and drainage of chest tube, symptoms at presentation and follow-up examination, and evidence of adverse reaction to talc instillation.
All chest tubes were placed by the radiologist using either sonographic (n = 23) or CT (n = 3) guidance. When the effusion was free-flowing, the skin insertion site was the mid or posterior axillary line with the tip of the tube directed toward the postero-inferior hemithorax. When the effusion was loculated, the tip of the tube was directed toward the dependent portion of the loculation. All tubes were placed using the modified Seldinger technique as follows: an 18-gauge trocar needle was placed into the pleural space. A 0.038-inch floppy-tipped wire was advanced well into the fluid collection. Sequential dilators (usually 8-, 10-, 12-French) were then used to prepare the tube tract. A 14-French self-retaining catheter (van Sonnenberg; Medi-Tech, Boston Scientific, Watertown, MA) was advanced over the wire into the pleural fluid. The pigtail catheter was curled and locked. At the time of placement, up to 1 L of fluid was initially evacuated, depending on patient comfort and symptoms, and the chest tube was placed at -20 cm H2O continuous wall suction via a water-seal device (Pleur-evac; Deknatel, Fall River, MA). A chest radiograph was then obtained to document the position of the chest tube. All patients were hospitalized for the duration of the procedure, and the tube output was recorded daily. Pleurodesis was performed when the 24-hr fluid drainage was less then 150 mL and chest radiographic findings confirmed little or no residual fluid. If the patient's tube output diminished, yet the chest radiograph showed an increase in fluid or evidence of loculation, 250,000 U of streptokinase in 100 mL of normal saline was injected through the catheter. The catheter was then clamped for 2 hr, and the patient was encouraged to change positions to distribute the solution uniformly. The tube was then opened and reconnected to the suction. If tube output did not increase and the fluid remained loculated, an additional dose of streptokinase was injected on each subsequent day until the tube output improved.
Immediately before talc administration, patients received 2 mg of IV morphine. The sclerosant was administered by the radiologist via a slow injection through the chest tube. Pleurodesis for the first three patients (12%) was performed with 10 g of sterile talc mixed with 10 mg of 1% lidocaine in 100 mL of normal saline. Because 5 g of talc has a similar efficacy in achieving pleurodesis and is thought to result in fewer complications than 10 g of talc [8,9,10], the dose was decreased to 5 g in the remaining 22 patients [1]. After instillation of talc, we clamped the tube and discontinued the suction for 2 hr as the patient rotated from supine to both decubitus positions every 15 min to aid distribution of the talc in the pleural space. Suction was resumed at -20 cm H2O for 24 hr followed by tube removal.
After tube removal, posteroanterior and lateral chest radiographs with the patient upright were obtained and served as the 1-day postsclerotherapy chest radiographs. In those patients who survived for 1 month or more, follow-up upright posteroanterior and lateral chest radiographs were obtained 30 days after sclerotherapy.
To assess the response to sclerotherapy, we compared the 30-day postsclerotherapy chest radiographs with the presclerotherapy baseline and the 1-day postsclerotherapy chest radiographs. The response at 30 days was defined as complete (no reaccumulation of pleural fluid since the 1-day postsclerotherapy radiographs), partial (reaccumulation above the 1-day postsclerotherapy level but still below the presclerotherapy level), or no response (reaccumulation to or above the presclerotherapy level). Total volume and duration of catheter drainage was also noted.
The Fisher's exact test was used to examine whether there was an association between the response rate and the presence of ascites, the amount of ascites, the size of initial pleural effusion, and the location (unilateral or bilateral) of the pleural effusion. Logistic regression analysis was used to examine whether the response rate was associated with chest tube duration or with the chest tube output. Wilcoxon's rank sum test was used to examine whether ascites affected the chest tube duration or the chest tube output.
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At 30 days, 10 of 13 patients with 11 of 14 treated effusions had a complete response to sclerotherapy, and one patient with one treated effusion had a partial response. Thus, 11 (85%) of 13 patients with 12 (86%) of 14 treated effusions had a complete or partial response to sclerotherapy, and all 11 patients reported improvements in pain and shortness of breath. One of the patients who had a complete response had a loculated pleural effusion that required infusion of 250,000 U of streptokinase in 100 mL of normal saline. Eleven of the 12 treated effusions that had a partial or complete response required only one instillation of talc. One of the treated effusions that had a complete response required two 5-g talc instillations through the same tube on consecutive days because of increased fluid drainage after the first instillation.
Two patients had no response to sclerotherapy. Both patients had bilateral effusions; the treated effusions were large (n = 1) and moderate (n = 1), with small contralateral effusions in both. In one of these patients, after initial symptomatic improvement after tube drainage, pleural fluid reaccumulation occurred within 24 hr of chest tube removal, and symptoms of shortness of breath and chest pain recurred. The chest tube was replaced and talc sclerosis was repeated, but a 30-day follow-up showed no response to sclerotherapy. The second patient's pleural effusion was slow to resolve and recurred after sclerotherapy. The patient had no symptomatic improvement.
Of the 12 treated pleural effusions that had a complete or partial response, nine (75%) had associated ascites at the time of tube placement and three (25%) did not. Both effusions in the patients who did not respond to sclerotherapy had ascites. The amount of ascites did not affect response to sclerotherapy (p = 1.0). The presence of ascites did not affect response to sclerotherapy (p > 0.999), chest tube output (p = 0.659), or chest tube duration (p > 0.999). Response to sclerotherapy was not affected by the duration of chest tube drainage or chest tube output (p = 0.957, p = 0.791, respectively). Effusion size or location (unilateral or bilateral) also did not affect the 30-day response (p = 0.99, p > 0.999, respectively).
Adverse reactions to talc sclerotherapy were transient fever
(
39.2°C), lasting less than 24 hr within 8-24 hr after talc
instillation (n = 6) and mild to moderate pleuritic chest pain or
shortness of breath within 4 hr after the procedure (n = 3).
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Patients with gynecologic malignancies and pleural effusions can manifest with incapacitating dyspnea. Drainage of the pleural space can rapidly relieve symptoms in those patients who do not respond to systemic chemotherapy. Drainage is performed either by repeated thoracentesis or by thoracostomy, with or without chemical pleurodesis [32,33,34]. Because thoracostomy with small-bore catheters (gauge < 14-French) is safe, well tolerated by patients, and provides effective drainage, it is currently being used with increasing frequency to treat gynecologic patients manifesting with pleural effusions and dyspnea [1, 18, 35,36,37,38]. Imaging guidance is often used to direct optimal positioning of these tubes to drain the pleural space because the success of pleurodesis requires a nearly complete evacuation of fluid [39,40,41]. Although many sclerosant agents including biologic substances, antibiotics, antineoplastic agents, and radionuclides have all been used for pleurodesis, talc is the preferred agent because of its low cost, efficacy, and relatively low complication rate [1, 8, 32, 42].
We thought that chemical pleurodesis might be unsuccessful in the management of pleural effusions in patients with gynecologic malignancies and ascites. This presumption was based on our previous experience treating these patients; the similar experience of our referring clinicians; and pleurodesis was shown to be ineffective in patients with cirrhosis, ascites, and pleural effusion [2]. In our study, small-bore catheter thoracostomy and talc sclerotherapy were shown to be an effective treatment option in this population. The success rate in our study (86%) is similar to that reported by Marom et al. [1] who used catheter drainage and talc sclerotherapy to treat malignant effusions from nongynecologic malignancies. Interestingly, the average volume of pleural fluid drainage was also similar in both studies, although the mean duration of smallbore catheter drainage was slightly longer in our patients who had gynecologic malignancies. Furthermore, in our series, the presence or absence of ascites did not affect the response to sclerotherapy, the total amount of fluid drained, or the duration of tube drainage.
To our knowledge, our series is one of the largest yet reported regarding treatment of malignant pleural effusions in patients with gynecologic malignancies [17, 18] and is the first study reporting the use of imaging-guided catheter drainage and talc sclerotherapy to treat these patients. Nevertheless, our results are limited because of the small number of patients studied. This limitation is inherent in most studies assessing the response of patients with malignant effusions to pleurodesis because of the high mortality associated with this condition. In our study, 48% of the initial study population either died or was lost to follow-up within 30 days of pleurodesis, and thus their response to sclerotherapy could not be adequately evaluated. This 30-day mortality rate is, however, similar to that reported in other studies [1, 17, 35, 37, 38, 43]. Our patients were referred for treatment primarily on the basis of clinical symptoms of pain or dyspnea. Some studies have suggested that factors other than symptoms should be used to select patients for sclerotherapy. In particular, Burrows et al. [44] found that a score of greater than 70 on a pretreatment Karnofsky performance scale predicted a significantly improved survival rate 30 days after sclerotherapy. Thus, in future prospective studies a more careful patient selection may result in improved results from sclerotherapy.
An additional potential criticism of our study is that we evaluated the response only over a relatively short period of time—30 days. Although the short period may have increased the apparent success rate of the procedure, we did this so that we could directly compare our results with those of previous investigations [1, 17, 18, 34, 35, 37, 38, 42, 45,46,47,48,49,50,51]. Because most malignant effusions recur within the first month after pleurodesis and because of the high mortality associated with this condition, most other studies have also used the 30-day response rate as the benchmark for assessing treatment response [1, 17, 18, 34, 35, 37, 38, 42, 46,47,48,49,50,51]. Of these studies, few have reported results for longer than a 1-month follow-up [42, 48, 49], likely because of the small number of patients who survived longer than 1 month. For these reasons, the 30-day follow-up is considered the standard when assessing the efficacy of pleurodesis [45].
Many authors require tube output to fall below 100 mL/day before pleurodesis [35, 37, 50]. However, to the best of our knowledge, no large study has been performed to establish the ideal benchmark for tube output in this situation. The decision to sclerose because of tube output is an arbitrary one based on clinical experience. One could argue that our decision to sclerose when tube output was less than 150 mL/day (rather than <100 mL/day) may have affected our results. However, many authors have successfully performed pleurodesis when daily tube output never fell below the 100 mL/day benchmark [1, 38, 49, 51], and one small study showed no difference in the success rate between effusions sclerosed when tube output was less than 100 mL/day and those sclerosed when tube output was less than 150 mL/day [1]. In fact, the 150 mL/day benchmark was recommended in a recent review [52] and by the American Thoracic Society [53].
A further criticism of our study may be that the group of patients without ascites was small (n = 3). In fact, because ascitic fluid can flow preferentially into the pleural space without accumulating in the peritoneal cavity [3,4,5,6], even these three patients might have had undetectable ascitic fluid. Nevertheless, our results were comparable with those of a similar study [1] performed in patients with metastatic malignancies (mainly breast and lung cancer) that did not commonly result in ascites. Thus, we are justified in our conclusion that the presence of ascites does not adversely affect the results of tube thoracostomy and sclerotherapy in patients with gynecologic malignancies.
In conclusion, our experience suggests that imaging-guided catheter drainage and talc sclerotherapy are an effective treatment for patients with metastatic gynecologic malignancies and symptomatic pleural effusions. The presence of ascites does not adversely affect the overall success of the procedure and should not preclude therapy in such patients.
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