Due to the possible recurrence, an adequate pleurodesis is really necessary to reduce the rate of recurrence for postoperative patients with PSP [5, 17, 18]. Combination of pleural abrasion and chemical pleurodesis has become the recommendation for PSP patients . In our study, we found that OK-432 pleurodesis resulted in a significant decrease in the rate of prolonged air leak after VATS, as well as the incidence of ipsilateral recurrence. We then analyzed the role of OK-432 pleurodesis in PSP, and attempted to determine the risk factors influencing the recurrence. To our best knowledge, this is the first retrospective study to observe that prolonged air leak increases the risk of recurrence remarkably and OK-432 pleurodesis reduces the risk of recurrence.
The underlying benefits of OK-432 may be attributed to the inflammation reaction of pleural surface caused by the stimulation of OK-432. This effect reinforces the cutting edge of blebs, which are may occasionally missed during the first surgery, and may promote the pleura symphysis to prevent the recurrence of pneumothorax.
As was shown in above results, patients who received OK-432 pleurodesis had shorter duration of chest tube and hospital stays after the VATS, which were consistent with previous similar studies . It may be largely due to the shorter postoperative air leak. These results indicated that OK-432 was likely to provide better quality of life after surgery compared with unique mechanical pleurodesis. In both groups, just a few patients occurred unpleasant complications, including pleural detachment, hemothorax and empyema, but these complications had been resolved by thoracocentesis or closed-tube thoracostomy combined with antibiotics. No mortality occurred in our study. Consequently, we suggest that OK-432 pleurodesis is safe for PSP patients.
The primary side effects of the pleurodesis with OK-432 were chest pain and fever, which almost could be well-relieved by nonsteroidal anti-inflammatory medications (NSAIDs) [12, 20]. 38 of 124 patients suffered fever after OK-432 chemical pleurodesis, which was significant higher than the control. Fever is one of the most common complication, and it was regarded as a kind of response to inflammatory reaction from chemical pleurodesis. Several studies confirmed that tetracycline pleurodesis induced 9% − 81% of fever[21, 22]. Interestingly, fever spontaneously disappear after about 2 days by conservative measures in all these patients. As for chest pain, the majority of patients used NSIDs to relieve postoperative chest pain, and only a little proportion of patients needed different dose of meperidine to relieve severe pain. Prolonged air leak was another complication in this study (2.45% in OK-432 group and 19.24% in control group), which was lower compared to other analogous studies [23, 24]. By means of the instillation of OK-432 or fresh frozen plasma, all air leaks could be settled successfully.
Many chemical irritants, such as minocycline, tetracycline and talc, have been used to decrease the rate of recurrence or hasten the cutting edge of air leak in spontaneous pneumothorax patients[10, 13, 25]. OK-432 was chosen for chemical pleurodesis in our study because it was easily purchased, safe, relatively low-cost, and available.The reported recurrence rate after VATS bullectomy alone was 16.0% − 23.9% [23, 26]. Cheng-Hung How argued that the recurrence was noted in one patient in the OK432 group and none in the minocycline group during a median follow-up of 16 months . Moreover, another study showed that the rate of recurrent ipsilateral pneumothorax was 3.8% for PSP patients with high recurrence risk, who received pleural abrasion with minocycline . The recurrence rate of our study was 0.81% in OK-432 group, suggesting that OK-432 pleurodesis was an effective way to prevent the recurrence of PSP. What caused the recurrence? Maybe it was attributed to the regeneration of newly-formed bulla, especially around the previous resection site. During these reoperation procedures, we found more or less bullas on the apex of lung which were newly-formed or missed in the first operation.
A variety of treatment approaches were applied to reduce the recurrence [28, 29]. The best procedure has not yet been established. Researchers have devoted themselves to analysis the risk factors for recurrent pneumothorax after VATS. Our results indicate that sex, age, BMI, smoking history, pneumothorax site, pneumothorax size, blebs number and complication did not correlate with postoperative recurrence, but prolonged air leak (> 3days) increased the risk of postoperative recurrence. However, a recent report holds that absence of smoking history, comorbidities, previous surgery for ipsilateral spontaneous pneumothorax and hand stitching increase the risk of postoperative recurrence . To our best knowledge, this is the first case-control study to reveal that OK-432 after pleural abrasion reduces the rate of recurrence compared with single mechanical pleurodesis. So we carefully recommend that OK-432 chemical pleurodesis should be taken into consideration for SPS patients, especially if postoperative prolonged air leak occurred.
Some limitations should also be acknowledged. Firstly, there were differences in both groups about smoking history and operation time, which may influence the surgical outcomes at some extent. Secondly, the median recurrence time was 40 months in the control group, so the relatively short follow-up period possibly underestimated the recurrence rate. Thirdly, the level of opration was associated with the learning curve of VATS technique. Surgical levels vary from person to person, and the level of young surgeons is inferior to those senior in general. Moreover, 3 patients in the control group experienced persistent postoperative air leak (over 7 days) that resolved with chemical pleurodesis with OK-432, and no recurrence occurred in these patients, which may cause bias on the results. Finally, this was a retrospective, small, single-center study, and further prospective, randomized, long-term follow-up researches are needed to rigorously test the efficacy of this treatment.