If you don't remember your password, you can reset it by entering your email address and clicking the Reset Password button. You will then receive an email that contains a secure link for resetting your password
If the address matches a valid account an email will be sent to __email__ with instructions for resetting your password
Address for correspondence: Li-Han Hsu, M.D., Division of Pulmonary and Critical Care Medicine, Koo Foundation Sun Yat-Sen Cancer Center, 125 Lih-Der Road, Pei-Tou District, Taipei, Taiwan
Pleural fluid loculations or trapped lungs frequently render patients with symptomatic malignant pleural effusions (MPEs) unsuitable for pleurodesis. Thoracoscopic surgery or thoracotomy with decortication is generally not feasible for patients with a poor performance status. MPEs have augmented procoagulant and depressed fibrinolytic activity that contributes to fibrin deposition within the pleural space. The authors conducted an observational prospective cohort study to investigate the use of intrapleural urokinase (IPUK) for such patients and made a comparison with a historical control group.
Methods
Between March of 2000 and August of 2005, 48 consecutive patients with symptomatic MPEs with an average Karnofsky performance scale score of 46.7% were recruited. Dyspnea persisted with the presence of substantial residual loculated MPEs in 36 patients and trapped lungs in 12 patients, when the effectiveness of 8-French intrapleural catheter drainage had decreased despite regular saline flushes. Urokinase was instilled daily through the catheter at a dose of 100,000 IU diluted in 100 ml of normal saline for 3 days. Additional IPUK instillation was required upon partial improvement. The records and chest radiographs of another 52 patients with symptomatic MPEs had met these eligibility criteria between January of 1995 and February of 2000 and received saline flushes only were also reviewed.
Results
Immediate lung reexpansion and resolution of dyspnea was achieved in 29 of the 48 patients who underwent IPUK therapy (60.4%). The mean dose of urokinase instillations per patient was 360,000 IU. There were no major complications. A significant association of earlier intervention with the success of IPUK therapy was noted. Responders also had a significantly increased drainage within the 24 hours after the first dose of IPUK. Minocycline pleurodesis was subsequently performed for the 29 IPUK responders. Eighteen patients were followed up until death, with a median survival of 6.5 months. The other remained alive at the time of analysis with a median follow-up of 5 months. Two patients had an immediate failure of pleurodesis at 1 month. Three relapses occurred at 3, 4, and 7 months from pleurodesis, respectively. Twenty-three patients (79.3%) had lifelong pleural symphysis, including 21 having loculated MPEs and two having trapped lungs, respectively. Compared with the historical control group, the IPUK study group had significantly greater improvement on chest radiography and a shorter duration of pleural drainage.
Conclusion
These results suggest that IPUK is a safe and useful nonsurgical adjunct therapy for loculated MPEs or trapped lungs in medically inoperable cancer patients.
Intrapleural catheter drainage followed by pleurodesis is the procedure frequently required for appropriately selected patients with symptomatic malignant pleural effusions (MPEs).
However, even after appropriate drainage procedures have been conducted, the presence of fluid loculations by fibrous adhesion or trapped lungs typically limits lung reexpansion and renders these patients unsuitable for pleurodesis. Thoracoscopic surgery or thoracotomy with decortication is often deemed necessary to effectively treat such patients, but is often not suitable for patients with a poor performance status.
The alternatives include repeat thoracenteses and insertion of an indwelling intrapleural catheter. The former is associated with significant morbidities and the latter was frequently occluded by fibrin requiring regular saline flushes. Intrapleural instillation of fibrinolytic agents may dissolve the transitional fibrin and effect a successful subsequent evacuation of loculated MPEs or reexpand the trapped lungs. To the best of our knowledge, it would appear that very few reports of trials to assess the relative efficacy of the intrapleural instillation of fibrinolytic agents have been published to date.
Here, we present our results pertaining to the use of intrapleural urokinase (IPUK) for the treatment of loculated MPEs or trapped lungs in medically inoperable cancer patients. Comparison with a historical control group was also made. The relevant theories relating to the effectiveness of such a procedure are discussed.
MATERIALS AND METHODS
Patients
Between March of 2000 and August of 2005, 1485 consecutive patients were evaluated for pleural effusions at the Sun Yat-Sen Cancer Center, a 180-bed hospital in Taipei. Six hundred ninety-two patients were proven to have MPEs, defined by the presence of malignant cells on the thoracentesis without signs of infection or proven bacterial invasion of the pleural space. Among them, 345 patients exhibited symptoms of MPEs and were admitted for intrapleural catheter drainage. Complete lung reexpansion following pleurodesis was achieved in 220 patients. The other patients had either substantial loculated MPEs or trapped lungs when catheter drainage ceased to work despite regular saline flushes. Loculated MPEs were defined as fluid collections with septa seen on chest computed tomography and/or ultrasonography or air-fluid levels in the pleura on the chest radiograph. A trapped lung was suggested by mechanical restriction of the visceral pleura preventing lung expansion. Forty-seven patients underwent thoracoscopy or decortication. The remaining 78 patients were deemed medically inoperable after anesthesia and surgical risk assessments. They were categorized as American Society of Anesthesiologists physical status class III to V and considered for IPUK therapy.
Eligibility criteria to proceed to IPUK therapy consisted of persistent dyspnea in the presence of substantial residual loculated pleural effusions (Fig. 1) or trapped lungs (Fig. 2) that could not be resolved with catheter drainage. The locule walls or peels surrounding the trapped lungs were less than 5 mm in thickness. To confirm the contribution of the radiographic findings to clinical symptoms, the size of the residual pleural fluid collection or extrapulmonary air was deemed to necessarily occupy more than one third of the chest height on chest radiographs. Bronchoscopy was performed to exclude the possibility of endobronchial obstruction. The decision of whether to continue IPUK therapy or to proceed to surgery was made jointly by the attending physician, an anesthesiologist, a thoracic surgeon, and a pulmonologist.
FIGURE 1A 45-year-old woman suffered from a left-sided malignant pleural effusion 3 years after treatment of locally advanced right breast cancer (A). An 8-French self-retaining catheter was inserted. Poor lung reexpansion and loculated pleural effusions became evident on chest radiograph (B) and computed tomography (C) when the drainage ceased. Ultrasonography showed fibrinous septa in the pleural fluid (D). Urokinase was infused daily via an intrapleural catheter for the next 3 days. The fourth dose was given on the day after the repositioning of the catheter into the largest residual locule. A total of 400,000 IU urokinase was infused. Minocycline pleurodesis was undertaken on the fourth day after the administration of the final dose of intrapleural urokinase. Chemotherapy containing docetaxel (Taxotere) was instituted later. At 6-month follow-up, complete success of pleurodesis was noted with residual pleural effusions occupying less than 5% of the left hemithorax, as revealed by chest radiograph (E) and computed tomography (F).
FIGURE 2A 38-year-old woman became symptomatic for a right-sided malignant pleural effusion 2 years after treatment for bilateral breast cancers (A). An 8-French self-retaining catheter was inserted. A condition of trapped lung was noted on the chest radiograph (B) when the drainage decreased. Bronchoscopy excluded proximal airway obstruction. Following the infusion of 300,000 IU urokinase, the lung reexpanded partially (C). Complete lung reexpansion was achieved after the infusion of urokinase to a total of 600,000 IU (D). The expelled fibrins conglomerated and floated within the fluid collected in the drainage bottle (E).
Exclusion criteria included (1) patient age younger than 18 or older than 90 years; (2) the presence of a bronchopleural fistula or a bleeding diathesis; (3) a patient receiving anticoagulants or drugs eliciting platelet-antiaggregant effects; (4) certain medical conditions contraindicating the application of thrombolytic therapy, such as a history of stroke, intracranial neoplasm, cranial or spinal surgery, and such injury arising within 14 days of study commencement; and (5) major thoracic or abdominal surgery undertaken within 10 days of study commencement.
Methods
All patients underwent closed intercostal drainage using an 8-French self-retaining catheter (pigtail drainage tube; Create Medic, Yokohama, Japan) inserted into the lowest portion of the pleural fluid collection or the largest locule noted under ultrasound guidance. The drainage catheter was then connected to a water seal system (thoracic suction regulator; Ohmeda, Columbia, MD) and maintained under continuous suction at −20 cm H2O until the time of catheter removal. The catheters were flushed every 6 hours with 20 ml of sterile saline to maintain their patency.
Eligible patients were infused 100,000 IU urokinase (Green Cross, Osaka, Japan) in 100 ml of saline via the intrapleural catheter daily for three consecutive days. The catheter was clamped for 3 hours after the instillation of the drug was completed, then reopened to suction. Patients were encouraged to change position during treatment so as to facilitate the mixing of the urokinase with the pleural fluid. Urokinase was reinstilled if, after earlier instillations, residual fluid remained within the pleural cavity or extrapulmonary air was partially reduced but still able to be seen on chest radiography.
Assessment
Primary end point.
During IPUK therapy, patients were assessed for a favorable response as demonstrated by resolution of dyspnea and chest radiographic evidence of improvement. The level of dyspnea at rest was assessed using a vertical 100-mm visual analogue scale (VAS; 0 = no shortness of breath, 100 = the most severe shortness of breath possible) before catheter drainage and both before and after IPUK therapy.
Such assessment was commenced only when the investigator conducting the assessment was confident that the patient understood how to use the scale.
The most recent chest radiographs (posteroanterior and lateral views of the effusion site) taken before starting treatment with urokinase were compared with the chest radiographs taken on completion of the urokinase treatment. To maintain consistency of the comparison of the radiographic results, we adopted the scoring system proposed by Bouros et al.
in their study of patients featuring parapneumonic effusions. The dimensions of the pleural fluid loculations or extrapulmonary air spaces were estimated by measuring the two orthogonal maximal diameters of either the effusion or air space on chest radiographs. The overall reduction in dimension of pleural fluid volume or extrapulmonary air collections was categorized as being one of the following: 0 (no change), 1 (less than one-third improvement), 2 (improvement of between one and two thirds), and 3 (more than two-thirds improvement).
For patients who had a score of 3 for their level of radiographically determined improvement, infusion of minocycline (Lederle Parenterals, Carolina, Puerto Rico) for pleurodesis at a dose of 7 mg/kg was performed, provided that the pleural drainage had decreased to a level of less than 150 ml every 24 hours (including returned saline flushes) for two consecutive days.
Follow-up chest radiographs were obtained 1 month after initial radiographic investigation, and, on occasion, even later for patients who underwent pleurodesis. The relative success or failure of pleurodesis was determined according to the relevant definitions for treatment success as proposed by the American Thoracic Society and the European Respiratory Society Consensus Statement.
The volume of pleural fluid drained from the intrapleural catheter was also recorded daily as was the total volume of IPUK solution instilled into the pleural cavity. As most intrapleural fibrinolytics increase drainage volume through inflammation, not necessarily through better lysis of the pleural adhesions, the volume of pleural fluid drained was not considered an end point for the trial.
Venous blood was collected for the purposes of establishing prothrombin time (international normalized ratio), activated partial thromboplastin time, and the serum levels of fibrinogen, fibrin-degradation products, and d-dimers before and 24 hours after the IPUK therapy. The Institutional Review Board of Sun Yat-Sen Cancer Center approved this 5-year prospective study, and informed consent was obtained from all the patients to participate in this IPUK study.
Historical Control
We reviewed the records of another 330 consecutive patients with symptomatic MPEs from the same institution during a 5-year period (January of 1995 through February of 2000) before the study period. Among them, 52 patients had met the previously cited eligibility criteria. Forty patients had loculated MPEs and 12 patients had trapped lungs. All patients had a similar 8-French intercostal drainage catheter inserted and connected to a water seal system with continuous suction at −20 cm H2O. Only regular flushes of the catheter with 20 ml of sterile saline every 6 hours were performed when the pleural drainage had decreased to a level of less than 150 ml every 24 hours. The chest radiograph taken before removal of the catheter or discharge from the hospital was compared with the chest radiograph taken when the amount of pleural fluid drainage was less than 150 ml during the previous 24 hours.
Chest radiographs of both the IPUK study group and historical control group were evaluated independently by two radiologists using the scoring system previously described without knowledge of the group of the patient (i.e., blinded). For cases of interobserver disagreement, the lower score obtained was used.
Statistical Analysis
Results are expressed as mean values ± SD. Continuous variables were compared using the two-sample Student t test, whereas categorical variables were compared using the χ2 or Fisher's exact test. The one-sample Student t test was used to assess pre-IPUK versus post-IPUK changes of systemic fibrinolysis. A p value of <0.05 for comparisons was considered to represent statistical significance. All analyses were performed with the SAS software (version 8.02; SAS Institute Inc., Cary, NC).
RESULTS
IPUK Study Group
Forty-eight patients (30 women) were eligible for the study. Thirty-six had residual loculated pleural effusions, and the other 12 had trapped lungs when the drainage decreased. The mean age of the patients was 53.7 years (range, 22–87). The underlying malignancies included lung cancer for 22 patients, breast cancer for 19, and one case each of thyroid cancer, ovarian cancer, prostate cancer, colon cancer, malignant pleural mesothelioma, lymphoma, and hepatoma. The average patient performance status measured by the Karnofsky scale was 46.7% (range, 30%–70%). The extent of duration of the effusions at the time of drainage, as estimated by review of prior radiography was 85.2 ± 82.4 days in the 41 assessable patients.
Immediate response to therapy.
The mean dose of IPUK instillations per patient was 360,000 IU (range, 300,000 IU–900,000 IU). A chest radiographic improvement score of 3 (excellent improvement) was noted for 29 patients (60.4%), including 26 patients with loculated MPEs and three patients with trapped lungs; a score of 2 (moderate improvement) was seen for two patients; six patients reflected minimal improvement (a chest radiographic improvement score of 1), and 11 patients revealed no improvement (a score of 0). Resolution of dyspnea was noted for all patients subsequent to catheter drainage. The mean VAS scores corresponding to before catheter drainage and before and after IPUK therapy are shown in Figure 3. The mean VAS score during baseline conditions was 71.3 ± 6.9 mm, a value that decreased after catheter drainage (51.4 ± 7.7 mm; p < 0.001) for all patients. For the group featuring a chest radiographic improvement score of 3, the mean VAS score (51.3 ± 8.5 mm) was further reduced after administration of urokinase (31.2 ± 6.6 mm), a difference that achieved statistical significance (p < 0.001). There was, however, no significant difference in VAS score as a consequence of urokinase administration for the group featuring a chest radiographic improvement score of <3 (51.4 ± 6.6 mm versus 51.7 ± 6.7 mm; p = 0.21)
FIGURE 3The effect of drainage and intrapleural urokinase (IPUK) therapy on dyspnea for cancer patients with loculated malignant pleural effusions or trapped lungs. The mean levels of dyspnea as determined using a 100-mm visual analogue scale (VAS) before drainage (solid bars), after drainage (hatched bars), and after IPUK (open bars) are shown. The bars represent SDs. The data are shown for all patients (left) and divided according to whether IPUK therapy failed or succeeded (right).
The median drainage time was 13 days (range, 8–32) for the IPUK responders. The median duration of the pleural effusion drainage before starting IPUK therapy was 5 days (range, 3–18) for them. The patient requiring the intrapleural catheter in place for 32 days had a critical illness with prolonged pleural effusion drainage (18 days) before starting IPUK therapy. She received the maximum 900,000 IU urokinase totally. Complete lung reexpansion was achieved. The success of pleurodesis maintained at follow-up until her death 29 months later.
Table 1 illustrates the clinical characteristics of the two patient groups divided into either successful (a chest radiographic improvement score of 3) or failed IPUK (a chest radiographic improvement score of <3) categories. There appeared to be statistically significant intergroup differences for the age of pleural effusions. Responders also had a significantly increased drainage within the 24 hours after the first dose of IPUK.
TABLE 1Clinical Characteristics of the Two Patient Groups Divided by the Response to IPUK Treatment
The median survival of the whole cohort was 4.0 months (range, 2–29). Median survival did not differ significantly between responders (6.5 months) and nonresponders (3.0 months) (p = 0.24).
Treatment failure.
Among the 19 patients who had inadequate pleural fluid evacuation or lung reexpansion after IPUK, 14 patients needed repeat thoracenteses to relieve their dyspnea. The other five patients had an indwelling intrapleural catheter with drainage into a bag, but there was frequent fibrous occlusion requiring regular saline flushes and several revisions.
Complications of therapy.
Vital signs were routinely monitored for all patients, which remained stable throughout the study period for all patients. No bleeding, fever, anaphylaxis, or allergic reactions were noted for any patient. Also, there were no significant deviations of the parameters of systemic coagulation and fibrinolysis from their baseline values after intrapleural instillations of urokinase.
One-month follow-up.
For 29 patients with a chest radiographic improvement score of 3, IPUK therapy were followed by minocycline pleurodesis before the removal of the intrapleural catheter. The median time lapse between the last dose of IPUK and pleurodesis was 4 days (range, 2–8). At 1-month follow-up, successful pleurodesis was achieved for 27 patients (93.1%; complete success for 23 patients and partial success for four patients).
Long-term results.
Of the 27 patients with an immediate success of pleurodesis at 1 month, 18 could be followed up until death, with a median survival of 6.5 months (range, 2–29). The others remained alive at the time of analysis, with a median follow-up of 5 months (range, 3–22). Three relapses occurred at 3, 4, and 7 months after pleurodesis, respectively. Finally, taking into account the immediate failures and the observed relapses, 23 of the 29 IPUK responders (79.3%; complete success for 19 patients and partial success for four patients) had lifelong pleural symphysis, including 21 patients having loculated MPEs and two having trapped lungs, respectively.
Comparison with Historical Control Group
Baseline patient characteristics and pleural fluid analysis were matched in the IPUK study group and historical control group (Table 2). No patient in the historical control group had a chest radiographic improvement score of 3. A score of 2 was seen in four patients. Fourteen patients had minimal improvement (a score of 1), and the other 34 patients showed no improvement (a score of 0). The overall improvement in the chest radiographic score was 2.02 ± 1.30 for the IPUK study group and 0.42 ± 0.64 for the historical control saline group (p < 0.001). The mean increment of fluid drained was significantly greater in the IPUK study group (521 ± 405 ml versus 117 ± 40 ml; p < 0.001). The mean duration of pleural drainage was 13.0 ± 3.8 days in the IPUK study group and 17.9 ± 3.0 days (range, 14–33) in the historical control saline group (p < 0.001).
TABLE 2Comparison of Clinical Characteristics and Chest Radiographic Improvement between the IPUK Study Group and Historical Control Saline Group
IPUK (n = 48)
Control (n = 52)
p Value
Age, yr
53.7 ± 16.1
55.1 ± 14.3
0.64
Female/male
30/18
29/23
0.49
Karnofsky performance status
46.7 ± 8.1
47.9 ± 6.7
0.41
Loculated MPE/trapped lung
36/12
40/12
0.82
Pleural fluid analysis
pH
7.3 ± 0.1
7.4 ± 0.1
0.44
Protein, g/dl
4.6 ± 0.8
4.7 ± 0.4
0.45
Glucose, mg/dl
113 ± 32
115 ± 26
0.67
Lactate dehydrogenase, IU/L
1194 ± 1721
1048 ± 584
0.58
White blood cell count/mm3
793 ± 516
718 ± 391
0.81
Chest radiographic improvement, no. of patients
Score 3 (>66%)
29
0
Score 2 (<66%)
2
4
Score 1 (<33%)
6
14
Score 0 (0%)
11
34
Mean chest radiographic improvement score
2.02 ± 1.30
0.42 ± 0.64
<0.001
Mean increment of fluid drained, ml
521 ± 405
117 ± 40
<0.001
Mean drainage time
13.0 ± 3.8
17.9 ± 3.0
<0.001
Data presented are mean ± SD or number of cases. Student's t or χ2 test was used when appropriate. MPE, malignant pleural effusion; IPUK, intrapleural urokinase.
An imbalance between procoagulant and fibrinolytic activities within the pleural cavity could lead to abnormal fibrin turnover and pleural fibrin deposition for cases of MPE. According to the studies of Satoh et al.,
although the levels of urokinase-type plasminogen activator were noted to be elevated in the carcinomatous pleural exudates, the more substantially increased levels of inhibitors of these molecules, namely, plasminogen activator inhibitors 1 and 2, likely resulted in depressed fibrinolytic activity, favoring the deposition and maintenance of intrapleural fibrin.
Urokinase is a direct plasminogen activator and is not antigenic. In contrast to streptokinase, its fibrinolytic activity is not inactivated by anti-urokinase antibodies generated by exposure to prior urokinase therapy. IPUK has been reported to be able to decrease the viscosity of gelatinous pleural fluid, degrade fibrinous septae and adhesions, and débride the pleura of fibrinous sheets, thus allowing reexpansion of the lung to occur.
To the best of our knowledge, only two earlier observational case series reporting the application of intrapleural instillation of fibrinolytic agents for the treatment of MPE have been published in the relevant medical literature.
reported their retrospective study of the use of intrapleural streptokinase for the management of loculated MPEs in 10 patients. All responded to the administration of between 500,000 and 1,500,000 IU of streptokinase, reflecting a significant increase in the quantity of pleural fluid drained and radiographic improvement. Also in 1999, Gilkeson et al.
proposed the administration of IPUK as a technical innovation to treat 20 consecutive patients with a total of 22 MPEs, without mentioning the presence of loculations. Each patient received two to four doses of 125,000 IU of urokinase through the chest tube once the drainage output of pleural fluid had decreased to a level of <100 ml every 24 hours. As a consequence of this treatment rationale, 19 of 22 examples of MPEs were effectively drained. In this context, we report the largest case series in the literature and specify the more homogeneous study group at enrollment. Only medically inoperable cancer patients with symptomatic loculated MPEs or trapped lungs were included. IPUK was instilled daily at a dose of 100,000 IU in 100 ml of normal saline with an average of 3.6 instillations (range, three to nine). The doses and procedure of IPUK therapy were based on published experience pertaining to patients with parapneumonic effusions and empyema.
Excellent chest radiographic improvement was noted for 29 patients (60.4%); moderate improvement was seen in two patients, minimal improvement was seen in six patients, and 11 patients showed no improvement at all. The overall chest radiographic improvement was greater than that of the historical control saline group (Table 2). There were no major complications. Intrapleural instillation of urokinase does not appear to alter the parameters of systemic coagulation and fibrinolysis, which was consistent with a previous report.
Patient baseline characteristics were compared between responders and nonresponders to IPUK therapy (Table 1). The earlier that treatment was instituted, the more likely it was that the outcome would be favorable. Responders also had a significantly increased drainage within the 24 hours after the first dose of IPUK. These have become reliable clinical predictors of the outcome after IPUK therapy.
In contrast with parapneumonic pleural effusions or empyema, pleurodesis should be attempted to avoid pleural fluid reaccumulation for patients with symptomatic MPEs once the underlying lung has completely reexpanded after pleural drainage. The initiation of the coagulation cascade with an associated decrease in pleural fibrinolytic activity plays a critical role in the success of pleurodesis.
the remnant urokinase and its metabolites in the pleural space may counteract the action of an administered sclerosing agent if the time lapse between the delivery of both these agents is short. The median time lapse between the administration of the final dose of IPUK and the start of pleurodesis was 4 days in our study. Successful pleurodesis was obtained for 23 of the 29 IPUK responders (79.3%), with a median follow-up period of 6 months. Such results proved to be very comparable to the results of studies describing chemical pleurodesis using a tetracycline analogue.
For a single-center study, the numbers are respectable and the reproducible clinical judgment provided by a small team is an advantage. The historical control from the literature and ours described above had inadequate saline drainage.
Because of the short life expectancy of cancer patients with MPEs, we did not randomize to a control placebo (saline) group at the start of the IPUK study in view of ethics. In fact, the loculated MPEs or trapped lungs persisted despite regular intrapleural saline flushes of as much as 80 ml/day in our historical control group and the IPUK study group before urokinase instillation. Repeated ultrasonograms also documented the action of urokinase in breaking down fibrinous septae of loculated MPEs (Fig. 4), as Maskell and Gleeson
reported. It appears that urokinase is effective through the lysis of pleural adhesions and not through the volume effect.
FIGURE 4A 47-year-old woman with metastatic breast cancer presented with a right-sided symptomatic malignant pleural effusion. When drainage through an 8-French intrapleural catheter ceased, ultrasonography showed fibrinous septa preventing drainage (A). After 300,000 IU of urokinase was instilled intrapleurally, repeated ultrasonograms in the same position showed good lung reexpansion and documented the action of urokinase in breaking down fibrinous septae (B).
Our data show that IPUK is a safe and useful nonsurgical adjunct therapy for loculated MPEs and trapped lungs in medically inoperable cancer patients. Successful pleurodesis obviates the significant morbidities associated with repeat thoracenteses or insertion of an indwelling intrapleural catheter with frequent fibrous occlusion requiring regular saline flushes. The IPUK therapy does optimize the outcomes because unrelieved loculated MPEs or trapped lungs can lead to intolerable symptoms, severely reducing quality of life and, potentially, life expectancy. At variance with traditional dogma,
we believe that MPEs should not be considered a contraindication for IPUK therapy.
The median drainage time was 13 days for the IPUK responders in the study, which is comparable with that for patients with parapneumonic effusions and empyema in a recent large multicenter trial
and significantly shorter than that of the historical control group. Further studies to specify the dose of urokinase required for instillation therapy and to establish consensus regarding the indications, method, and timing of IPUK administration will likely further shorten the duration of drainage and hospital stay. Commercially available small-bore catheters can easily be introduced into the pleural space and are well tolerated in MPE patients with a short life expectancy. However, they clog routinely, particularly in the setting of viscous bloody pleural fluids.
If standard chest tubes (24–28 French) were placed, the majority of the trapped lungs in the series would probably have expanded. In addition, a tumor rind causing a trapped lung is a more significant problem and is not infrequent. It seems unlikely that IPUK would help this situation, which accounts for the significantly lower success rate of IPUK for patients with trapped lungs (three of 12, 25%) than those with loculated MPEs (26 of 36, 72.2%) (p < 0.001). A visual inspection of the pleural space and performance of pleural biopsies with a novel semirigid medical thoracoscopy under conscious sedation will be necessary before attempting IPUK therapy in the future.
The authors thank Dr. Andrew T. Huang for critical reading of the manuscript, Dr. Chia-Chuan Liu for surgical advice concerning referred patients, Michelle Wu and Yu-Yu Hsu for preparation of the manuscript and graphics.
REFERENCES
Light RW
Pleural effusions related to metastatic malignancies.
31612-9&id=gr1.jpg){kind=link}
31612-9&id=gr2.jpg){kind=link}
31612-9&id=gr3.jpg){kind=link}
31612-9&id=gr4.jpg){kind=link}