Biological pleurodesis with powder collagen at malignant pleural effusion

1. Biological pleurodesis with powder collagen at malignant pleural effusion A.Akopov, V.Egorov, V.Varlamov Research Institute of Pulmonology, Saint-Petersburg, Russian Federation

2. Objective • Malignant pleural effusions are a common medical problem. • Rapid recurrence of pleural effusions requires repeated thoracocentesis, therefore increasing the risk of complications. • For these reasons the increasing distribution therapy by introduction in a pleural cavity of various sclerosing agents (talc, tetraciclin, bleomicin etc.) with the purpose of obliteration of a pleural cavity and exudation discontinuance.

3. Objective • Research Institute of Pulmonology has wide experience in application of the biological agent - powder collagen - for achievement of pleural obliteration in patients with spontaneous pneumothorax. • Collagen is a natural biopolymer functioning as a temporarily directing skeleton for regeneration which is gradually replaced with organism's own fabrics. • Tests of collagenic pleurodesis induction performed on dogs resulted in the full and uniform obliteration of dogs' pleural cavities. Results of histological examination showed that collagen sprayed in a pleural cavity caused sharp fibrinotic pleurisy without stimulating exudation. Varlamov V.V. et al, ERJ, 1990

4. Objective • Experiments on 47 mongrel dogs (irritative effects on the pleura)

5. Objective • Comparison of recurrences in 297 patients with primary spontaneous pneumothorax

6. Patients • 45 patients with malignant pleural effusions and expected survival of > 1 month (January 1997 to December 2002) • 19 men and 26 women at the average age of 64,3 years • Malignant pleural effusions were proved by cytological examination (20 patients) or pleural biopsy (25 patients) • Primary tumors were: lung cancer - 22 patients (0,49) breast cancer - 17 patients (0,38) ovarian cancer - 4 patients (0,09) prostate cancer - 2 patients (0,04)

7. Patients • Side of effusions right-side effusions - in 22 patients (0,49) left-side effusions - in 20 patients (0,44) bilateral effusions – in 3 patients (0,07) • Complaints dyspnea – 45 patients tachycardia - 39 patients pain - 35 patients • All patients previously received systemic chemotherapy which did not affect the effusions

8. Method • Powder collagen was derived from the cattle skin. The size of particles did not exceed 0,1 mm. The powder collagen was sterilized by placing it into 1% nitrofurilacrolein solution for 12-hours with consequent gamma-wave irradiation for 3-hours. • The collagen was verified sterile using the biological indicators.

9. Method • In all patients videothoracoscopy were carried out under general endotracheal narcosis and one-lung ventilation. • After visualisation of a pleural cavity, complete evacuation of all remaining fluid and estimation of the potential for lung reexpansion, 1 g of powder collagen was insufflated under pressure of 0,2 atm. • At the end of the operation two drainage tubes were installed. • The tubes were kept under suction (25 cm H2O) and drainage was resumed until the fluid effused was less than 100 mL per day.

10. Method • Responses were classified as: complete response (CR) at absence of clinical and radiological recurrence; partial response (PR) at the absence of clinical while at the presence of radiological fluid reaccumulation which did not require additional intervention; failure(F) – reaccumulation of fluid causing symptoms or requiring thoracocentesis. • All patients were called in for an examination every 3-months. They all had a thorough clinicoroentgenological examination in order to administer (if necessary) any additional thoracocenteses within the first year.

11. Results • The mean volume of pleural fluid drained before videothoracoscopy was 2,2±0,7 L (ranged from 1,3 to 3,4 L). • The average duration of the operations was 24 min (ranged from 17 to 47 min). Endotracheal tubes were removed in the operating room from all patients. • The early postoperative period proceeded without serious complications and deaths. • The average duration of drainage after operation was 2,7 days (ranged from 1,5 to 7 days) • The average postoperative hospital stay was 7,0±0,5 days (ranged from 4 to 14 days).

12. Results • Temporary temperature rise occurred in 4 patients (0,09) within first three days did not exceed 38°C. • No major chest pain symptom developed after the operation. • The toxic effects connected with collagen dispersion were not marked. • Dyspnea and cough were significantly reduced by the procedure. • All patients were discharged from hospital in good condition.

13. Results • Median survival after pleurodesis induction was 5,5 months for the patients with lung cancer and 9,1 months for the patients with breast cancer. • To sum up, at the follow-up in 12 months there were 5 patients with recurrences of effusion (0,11). • In 40 of 45 patients (0,89) who underwent thoracoscopic collagen insufflation reaccumulation of pleural fluid was not registered and additional thoracocentesis was not required.

14. Results • In 1 month (45 patients alive) CR - 43 (0,96), PR - in 2 (0,04), F - 0 • In 3 months (41 patients alive) CR - 29 (0,71), PR - in 10 (0,24), F - 2 (0,05) • In 6 months (27 patients alive) CR - 16 (0,59), PR - in 7 (0,26), F - 4 (0,15) • In 12 months (11 patients alive) CR - 10 (0,91), PR - in 1 (0,09), F - 0

15. Conclusion Videothoracoscopic powder collagen insufflation is simple, safe and effective method of biological pleurodesis induction in malignant pleural effusions, which allows achieving response and preventing relapses of fluid accumulation in a pleural cavity in the majority of patients.