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Eur J Cardiothorac Surg 2005;28:750-753
© 2005 Elsevier Science NL
Research Institute of Pulmonology, Pavlov Medical University, 12 Roentgen Street, Saint-Petersburg 197089, Russia
Received 22 February 2005; received in revised form 8 July 2005; accepted 8 July 2005.
* Corresponding author. Tel.: +7 812 2384826; fax: +7 812 2349046. (Email: akopovand{at}mail.ru).
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Abstract |
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 Top Abstract 1. Introduction2. Materials and methods3. Results4. DiscussionReferences |
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Key Words: Malignant pleural effusions • Collagen • Pleurodesis
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1. Introduction |
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TopAbstract1. Introduction2. Materials and methods3. Results4. DiscussionReferences |
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Various sclerosing agents such as talc, tetracycline, and bleomycin were used for obliteration of pleural cavity and cessation of the process of exudation [2–4]. These methods are relatively simple and proved effective.
Authors of this article have previously developed and introduced a new agent—collagen powder—administered into the pleural cavity to achieve its obliteration in patients with spontaneous pneumothorax [5,6]. Collagen represents a family of natural proteins acting in such circumstances as a temporarily structure which is gradually replaced with organism's own fibrous tissues [7]. The ability of collagen powder to disperse evenly in closed spaces, such as the pleural cavity, has been confirmed by aerodynamic investigations. Histological findings proved that intra-pleural collagen caused acute non-exudative fibrinous pleurisy. Pleural inflammatory reaction to collagen appeared minor as all inflammatory effects subsided by the end of the first week and adhesions consisting of mature connective tissue were formed in 2 weeks after administration of the agent [5]. Lung compliance and morphology also remained normal.
The aim of this prospective study was to analyse the results of collagen pleurodesis in patients with malignant pleural effusions.
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2. Materials and methods |
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TopAbstract1. Introduction2. Materials and methods3. Results4. DiscussionReferences |
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Collagen was produced in the experimental laboratory from cow skin and such bovine dermal collagen was not commercially available at the time. No animal was slaughtered solely for the purpose collagen production. It was manufactured in the form of powder with the size of particles not exceeding 0.1 mm. Sterilisation of the agent was achieved by placing it into 1% nitrofurilacrolein solution for 12-h followed by exposure to 
-radiation for 3-h. Sterility was subsequently confirmed microbiologically when no growth of common pathogens (Bacillus subtilis, Staphylococcus aureus, Escherichia coli, Candida albicans) was observed after a standard period of incubation.
The indications to collagen pleurodesis were re-accumulation pleural fluid after a formal drainage and failure to respond to systemic chemotherapy. In cases of bilateral effusions induction of pleurodesis was carried out at the most affected side. Thoracoscopy was performed under general anaesthesia and ventilation of the contra-lateral lung. After thoracoscopic inspection of the pleural cavity and evacuation of all remaining fluid 1 g of powder collagen was insufflated into the pleural cavity under pressure of 0.2 atm. Two chest drains were then positioned and kept on suction aspiration (
25 cmH2O) for 48 hours or until the amount of discharge reduced to less than 50 mL daily. pH of the drained fluid was also measured taking into the account the previous reports of its predictive value on survival [9].
Patients were observed in the hospital for at least 5 days after the procedure to allow comprehensive assessment of potential immediate side effects and early complications. Subsequent outpatient follow-up took place at 3-monthly intervals and consisted of the clinical review and chest radiography. None of the patients was lost to follow-up.
The outcome of collagen pleurodesis was defined as a complete response in the absence of clinical and radiological features of recurrence of pleural effusion, partial response when fluid was evident radiologically but lack of symptoms required no additional intervention, and a failure, when re-accumulation of fluid was symptomatic and/or required repeat thoracocentesis.
The differences between the above clinical outcome groups across the pleural fluid pH variable were assessed using 
-square tests and Fisher's Exact Test, as appropriate. Statistical analysis was carried out using SPSS, version 12.0, computer software programme (SPSS, Chicago, Illinois, USA). P<0.05 was considered significant.
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3. Results |
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TopAbstract1. Introduction2. Materials and methods3. Results4. DiscussionReferences |
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Surgical intervention took on average 24 min to perform (ranged from 17 to 47 min) and was followed by immediate extubation of all patients.
There were no serious complications in the early postoperative period. None of the patients died. Full lung re-expanded was achieved within 1–5 days. The maximum duration of post-operative chest drainage was 7 days and on average all drains were removed within the first 2, 7 days (Table 1 ). Side effects of the treatment were minor. Short-lasting low-grade pyrexia developed in 4 (9%) patients but no other systemic side effects related to collagen administration were observed. Chest pain experienced by the patients was not severe enough to require opioid analgesia. None of our patients experienced nausea and vomiting. Dyspnoea and cough were greatly reduced after the procedure. On average the patients stayed in the hospital for 7 days (range from 5 to 14 days) and had clinical and radiological evidence of complete resolution of pleural effusion at the time of the discharge.
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Fig. 1 illustrates the outcome of thoracoscopic collagen pleurodesis. All 45 patients remained free of pleural fluid for more than a month. In 3 months after the operation, 2 out of 41 (5%) alive patients needed repeat thoracocentesis and at 6 months 4 of 27 (15%) alive patients required further evacuation of fluid. In 1 year, the outcome of pleurodesis in 10 out of 11 (91%) alive patients was classified as a complete response, and 1 patient had a partial response. In summary, out of all treated patients only five (11%) developed recurrent malignant pleural effusion and required its repeat drainage at some point during the follow-up period. In the vast majority (89%) patients thoracoscopic collagen pleurodesis proved successful in complete and permanent resolution of fluid collection.
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4. Discussion |
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TopAbstract1. Introduction2. Materials and methods3. Results4. DiscussionReferences |
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Chemical pleurodesis is the treatment option used most often for the control of symptomatic malignant pleural effusions. Its efficacy is attributed to an inflammatory response to the administered chemical agent resulting in mesothelial injury, decreased fibrinolytic activity and stimulation proliferation of fibroblasts [11]. The process of pleurodesis can also be triggered without significant inflammation. For example, Lee et al. [12] advocated the use for this purpose transforming growth factor (TGF)-beta2, which is profibrotic cytokine proved capable of producing fibrosis without inducing pleural inflammation in sheep. Collagen as a biological material is widely utilised in the form of xenograft across the range of surgical specialities [7,13] and one of the authors successfully used commercially available porcine dermal collagen mesh in anterior abdominal wall reconstruction. Obviously, the powder form bovine dermal collagen in our series was the only practical way to deliver and achieve its even distribution throughout the closed space of pleural cavity. The principle of collagen administration into the pleural cavity is unique as the substance not only stimulates the growth of connective tissue, but also represents an integral component of such tissue [14]. This principle has never been previously applied to the treatment of pleural effusions. Our reported experimental studies and clinical experience with intra-pleural insufflation of collagen powder in patients with spontaneous pneumothorax have proved the efficiency and long-term safety of this method [5,6]. However, in most cases of spontaneous pneumothorax there is no extensive injury to the pleura in comparison with carcinomatosis when it is affected by multiple metastatic nodules and lymphangitis. The outcome of collagen pleurodesis in these conditions has not been studied.
Talc, tetracycline, doxycycline, and bleomycin are among the primary sclerosing agents reported to induce pleurodesis. Unfortunately, as often the case in medical literature, comparison between the published series is difficult due to different length of follow-up and definition of successful outcome. Most institutions consider that the treatment fails if additional thoracocentesis is required within 1 month after the procedure [4]. The response to the above agents varies from 60 to 96% [3,15,16] and talc is regarded the most effective [17,18]. Talc, when administered in the form of powder into the pleural cavity, is not without potential respiratory complications, such as acute pneumonitis, empyema, and adult respiratory distress syndrome (ARDS) [4]. Systemic migration of talc is blamed as a possible mechanism for ARDS. Doxycycline can lead to pain syndrome and multi-locular pleural collections in up to two-thirds of patients, who as the result require prolonged treatment and opioid analgesia [2]. Cytotoxic antibiotic bleomycin commonly causes dermatological and pulmonary toxicity, troublesome mucositis, fever and renal impairment [3]. We observed none of the above complications after intra-pleural administration of collagen powder. No other serious complications were apparent, despite of the significant medical co-morbidity in many of our patients.
Adequate fluid drainage is essential prior to administration of a sclerosing agent and failure to achieve it is often the reason for incomplete lung re-expansion indicating multi-locular nature of effusions and trapped lung [1]. We observed no difficulties in achieving expansion of previously collapsed lung providing all pleural fluid was completely evacuated before collagen administration.
This study suggests high efficiency of thoracoscopic collagen pleurodesis as good clinical and radiological response was achieved in all patients. All patients remained free of pleural collections for more than 1 month. Long-term benefit was observed not only in those with the complete response, but recurrences in those with the partial response were also asymptomatic and did not necessitate repeat thoracocentesis. Out of all treated patients only five (11%) developed recurrent malignant pleural effusion and required its repeat drainage at some point during the follow-up period. In the vast majority (89%) patients thoracoscopic collagen pleurodesis proved successful in complete and permanent resolution of fluid collection.
It was reported that pleural fluid pH could predict the success or failure of pleurodesis [9]. It is believed that the increased acidity of the fluid is associated with high pCO2 and lactate concentration and metastastatic disease on mesothelial surface block the efflux of glucose and other metabolites from the pleural space. However, we were unable to confirm statistically significant correlation between the pleural fluid pH and the outcome of pleurodesis, similar to findings by Heffner et al. [19] on meta-analysis of more than 400 patients. Contrary to findings by Burrows et al. [20], we found that pleural fluid pH of less than 7.3, as measured in almost half of our patients with malignant pleural effusions, was associated with poor survival (P<0.05).
In summary, thoracoscopic insufflation of bovine dermal collagen powder is a simple, safe and effective method of pleurodesis in patients with malignant pleural effusions.
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References |
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TopAbstract1. Introduction2. Materials and methods3. Results4. DiscussionReferences |
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