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We analyzed chemical pleurodesis role in recurrent neoplastic pleural effusions management, performed by two different techniques: VATS and minimal lateral thoracotomy. We compared the results obtained using the two different procedures, and we also evaluated the two sclerosing agents used (talc and alcohol). From January 1987 to March 2002, we treated 565 patients with malignant pleural effusion: 355 (63%) by VATS and 210 (37%) through mini-thoracotomy all of them underwent chemical pleurodesis: 442 (78%) by means of talc and 123 (22%) by alcohol. Chemical pleurodesis therapeutic success was globally obtained in 436 patients (77%). Dealing with surgical approaches, VATS reduced operating time (33 versus 44 minutes: P < 0.001), mean drainage time (3 versus 5 days: P < 0.001), complications (2% versus 7%: P = 0.006) and mean postoperative course (5 versus 7 days: P < 0.001). Therapeutic success of VATS-treated patients was 81% versus 65% of those undergoing thoracotomy (P < 0.001). We obtained a significantly lower relapse rate in the patients of all the two groups treated with talc versus alcohol (12% versus 35% in VATS group and 25% versus 59% in thoracotomic group). Our data indicate that chemical pleurodesis represents a good palliative treatment of neoplastic pleural effusion. Talc was superior to alcohol as sclerosant agent regardless of the surgical procedure. Comparing the two techniques, VATS should be preferred to minimal thoracotomy. We can suggest talc pleurodesis by VATS as the choice treatment in case of recurrent pleural effusions.