Spontaneous pneumothorax rates following video‐assisted thoracoscopic talc pleurodesis with or without resection of macroscopic bullous disease

Recurrent primary spontaneous pneumothorax (PSP) is routinely treated by video‐assisted thoracoscopic (VATS) talc pleurodesis (with or without localized resection of macroscopic bullous disease). There is a paucity of published data regarding durability of the procedure and the rate of recurrent pneumothorax after such surgery, and this has significant implications from a prognostic and employment limitation perspective.


Introduction
A spontaneous pneumothorax can be defined as the occurrence of a pneumothorax in the absence of thoracic trauma. 1 Such pneumothoraces are classified as primary or secondary depending on the presence or absence of an underlying lung disease. 2,3Primary spontaneous pneumothorax (PSP) occurs in the absence of clinically apparent pulmonary parenchymal or airways disease or trauma, and secondary spontaneous pneumothorax (SSP) occurring in the presence of a underlying lung disease, most commonly chronic obstructive airways disease. 1,3PSP has a recurrence rate of 32% within the first 12 months. 4When treated with chest tube drainage alone, the recurrence rate of ipsilateral spontaneous pneumothorax is between 26.1% and 50.1%, 5 increasing in probability with subsequent episodes, particularly when these occur within 2 years of the initial occurrence. 6There are various accepted treatment modalities for PSP, ranging from observation to surgical intervention. 7Surgical intervention is the course of management utilized when conservative measures fail to rectify the pneumothorax, or if a subsequent second episode occurs. 8Accepted indications for surgical intervention include the occurrence of a second ipsilateral pneumothorax, a first contralateral pneumothorax, a synchronous bilateral spontaneous pneumothorax, a persistent air leak (despite 5-7 days of chest tube drainage) or failure of lung reexpansion, a spontaneous hemothorax, an at-risk professions (e.g., pilots, divers) and a pneumothorax occurring during pregnancy. 2here are various surgical approaches for the treatment of PSP but since the introduction of video-assisted thoracoscopic surgery (VATS), this has become the accepted approach. 2,8There are a number of surgical techniques that can be utilized to induce pleural symphysis and obliteration of the pleural space including pleural abrasion, chemical pleurodesis with agents such as talc, Povidone iodine and minocycline, and parietal pleurectomy.In addition to these interventions, surgeons also perform resection of areas of the lung with obvious macroscopic subpleural cyst or blebs.
This retrospective study sought to ascertain the rate of ipsilateral recurrent pneumothorax and contralateral primary spontaneous pneumothorax in patients who had undergone VATS talc pleurodesis (with or without lung resection) over a 15-year period.

Patients
Patients for this study were sourced from a departmental database, National Thoracic Surgery database, and case note review as consecutive cases from a single department working across both private and public hospitals.
One hundred and seventy-seven patients were included in this study with 85% of cases from one surgeon and the remainder of cases conducted by a second surgeon.In total, 47 were female (26.55%) and 130 were male (73.45%).There were 18 active smokers in the male group (13.8%) and 6 in the female group (17.6%).The study included 157 patients with recurrent primary spontaneous pneumothorax (88.7%), 8 with primary tension pneumothorax (4.7%), and 12 with a primary spontaneous pneumothorax which failed to resolve after 5 days of conservative treatment (6.8%).It is worth noting there is no literature to support operating after the first spontaneous pneumothorax when the presentation is with a tension pneumothorax, but it is the practice of one of the surgeons, particularly in patients who live and work remotely, which was not uncommon in South Australia.
Patients who presented with a single primary spontaneous pneumothorax were precluded from this study.All underwent surgical intervention between June 2001 and November 2016, either VATS talc pleurodesis alone (114) or VATS talc pleurodesis and wedge pulmonary resection (in cases of macroscopic subpleural bullous disease).Patients were followed up by telephone interview to determine the presence or absence of an ipsilateral recurrence.

Surgical methods
After induction of general anaesthesia, single lung ventilation was achieved with a double-lumen endotracheal tube.Tube position and lung isolation were confirmed and the patient was placed in the lateral decubitus position.A lateral thoracic support was placed under the contralateral hemithorax to stabilize the patient and increase intercostal space size on the operative side.A single-shot paravertebral injection of 0.5% Bupivacaine was placed at 3-4 locations between T3 and T6.The operative lung was isolated and isolation reconfirmed.
Two 1-cm incisions were placed in the fifth or sixth intercostal space between the anterior and mid-axillary lines.A 10-mm diameter 30 laparoscope was introduced and the lung and hemithorax thoroughly examined.Macroscopic pulmonary subpleural cysts (defined as visible cysts greater than 1 mm in diameter) were identified.If these were located in the apical segments of the upper or lower lobes, a pulmonary parenchymal wedge resection was performed (utilizing and additional 1 cm port in the fifth or sixth intercostal space in the posterior axillary axillary line).The wedge resection was performed using either Covidien Universal 3.5 mm or an Endo GIA 3.5 mm device.Following wedge resection(s) sterile talc (5 g, Orion Laboratories, Western Australia) was insufflated using a manual insufflation device to achieve coverage of all exposed visceral and parietal surfaces.A single chest drain (28 Fr Mallinkrodt or 24 Fr Blake drain) was inserted via the anterior most port and positioned apically.The lung was visually observed to reexpand and the wounds closed in layers.
Patients were then managed with underwater seal drainage on suction (À20 cm H 2 O) for a period of 24 h and free drainage for a further 48 h.

Statistical methods
The recurrence data were censored at 48 months.Cox regression model analysis was used to examine the difference in recurrence rate between talc pleurodesis and wedge resection group and the talc pleurodesis without wedge resection group after adjustment for the age at the surgery.Proportional hazard assumption was assessed using Schoenfeld residuals.All analyses were performed using Stata 15.1 (StataCorp, Texas, USA).Statistical significance was assumed with a P-value of less than 0.05.

Results
This study analyzed the outcomes of 177 patients who underwent a surgical procedure for spontaneous pneumothorax.This included 114 patients who underwent a VATS talc pleurodesis and 63 who underwent a talc pleurodesis and wedge resection of diseased lung.A wedge resection was performed when a parenchymal bulla or distinct, well circumscribed area of bullous disease was identified at the time of surgery.In all cases where wedge resection was performed, bullae were measured at 1 mm in diameter or greater, and in 62 of the 63 cases (98.4%) these were present in clusters of three or more in the apical segment of the upper lobe.In one case, the area of bullous disease was located at the superior peri-fissural aspect of the lower lobe.
The time from mean time procedure to drain removal was recorded as the postoperative day on which the drain was removed.This was similar in both groups, 2.94 days in the talc pleurodesis only group and 3.0 days in the talc pleurodesis/wedge resection group (P = 0.21).
There were no wound or pleural space infections in either group and the mean length of postoperative stay was 4.2 days in the talc only group and 4.0 days in the talc pleurodesis /wedge resection group (P = 0.24).The median follow-up time was 48 months for talc pleurodesis alone group and 38.93 months for wedge resection group.The median age was 24.9 years old (IQR = 21.1-31.5)for the talc pleurodesis alone group and 24.3 years old (IQR = 21.1-32.3)for the wedge resection group.A total of 72.8% (N = 83) were male in talc pleurodesis alone group and 74.6% (N = 47) were male in wedge resection group.There was one recurrent ipsilateral pneumothorax in a patient who underwent talc pleurodesis only (0.9%), and no ipsilateral recurrences in the wedge resection group.There were 10 contralateral recurrence in total at 48 months (5.6%), 5 in each group (recurrence rate of 4.5% and 11.6% for talc pleurodesis alone group and wedge resection group, respectively).Using Cox regression model after adjustment for age at the time of surgery, there was no significant difference in recurrence rate between the two study groups (HR = 2.14, 95% CI = 0.61-7.5,P = 0.233).These recurrent pneumothoraces occurred at mean of 15 months postoperatively and no new pneumothorax occurred beyond 48 months.
Post-hoc power analysis was performed and the study had 52.4% power.Assuming s 1 = 0.96 and s 2 = 0.88, 370 patients (185 per group) 30 events would be required to achieve 80% power at 5% significance level.
The patient with the recurrent pneumothorax after talc pleurodesis was identified in the postoperative clinic at 14 days.A repeat VAT was performed and it was documented that there was minimal evident inflammatory pleural response to the talc.A parietal pleural abrasion was performed and the patient was discharged on day 3 postoperatively without complication.
Of the patients with new contralateral pneumothorax in the 48 month follow-up period, 6 underwent surgery and 4 were treated conservatively.The decision to operate was made based on the past pneumothorax history.Four patients declined surgery at that stage.
The operative procedures were all VAT talc pleurodesis as no macroscopic bullous disease was identified at the time of the procedure.

Comment
The durability of the various surgical interventions for recurrent spontaneous pneumothorax had not previously been wellestablished despite these interventions being in common use for more than 30 years.Ipsilateral recurrence rates in the order of 3%-7% have been reported, 9 significantly higher than the single case in this series.Furthermore, there is no definitive level 1 data on the incidence of contralateral primary spontaneous pneumothorax following surgical intervention in this group.This uncertainty has long been a complicating factor in the provision of accurate advice to patients as it pertains to subsequent employment restrictions and the ongoing risk associated with activities such as scuba diving, and high altitude sky-diving.
This study has demonstrated that videoscopic talc pleurodesis with or without the resection of bullous regions of the upper lobe is a durable therapeutic option that prevents recurrent ipsilateral pneumothorax in the long term.This study also demonstrated that a significant number of patients (5.6%) develop a new contralateral pneumothorax within the 2 years of their initial surgical intervention, irrespective of the presence or absence of macroscopic bullous disease on the operative side.
There has been uncertainty surrounding the rates of postoperative recurrence and subsequent spontaneous contralateral pneumothorax, complicating the provision of accurate advice to patients as it pertains to subsequent employment restrictions and the ongoing risk associated with activities such as scuba diving, and high altitude sky-diving.This raises the question of the need for prophylactic surgical treatment of the contralateral lung in all patients with a history of surgical intervention for primary spontaneous pneumothorax.This decision is relatively straightforward in cases where the patient is in a high-risk occupation, lives or works in a remote location, or plans to do so for an extended period of time, where the risk benefit ratio is sufficiently high.For all other patients, the decision is less clear.As there were no cases of macroscopic bullous disease in the contralateral pneumothorax group in this study, we could not comment on the significance of radiological evidence of such as an independent risk factor for pneumothorax in this group.This may be a reflection of sample size, and there is some evidence in similar studies that the presence of contralateral bullous disease on high resolution CT is a risk factor for subsequent pneumothorax. 10In our institution the significant ongoing risk of contralateral pneumothorax is discussed and treatment offered if requested.
Due to the aim of analysing the ipsilateral recurrence rates and rates of contralateral spontaneous pneumothorax post VATS talc pleurodesis, an analysis of postoperative complications such as infection were not within the scope of this study.This being said, it was noted that there were no cases of talc pneumonitis in patients with a primary spontaneous pneumothorax reported by the surgeons involved.
There are limitations presented from this research.Due to the timeframe of a 4-year follow up, a conclusive argument cannot be substantiated based on the necessity for a longer span between the operation and the follow up.The designation of a 4-year follow up was based upon accessing more data, which were closer to the date of this paper's origination, and as such we could not extend the follow up period any further in order to standardize the data.To more accurately depict the incidence of recurrent rates, longer follow up margins are necessary in future research.Another limitation to this study is the number of participants, which led to an underpowered post-hoc calculation, as well as a greater number of patients lost to follow up beyond 36 months in the talc plus wedge group leading to a difference in median follow up.Due to this, there is limited information to depict the difference between the two treatment groups.Further research should aim at acquiring a larger data pool, with potential cross institutional data in order to establish a stronger correlation.

Full
ethics approval was obtained from the The Central Adelaide Local Health Network Human Research Ethics committee (CALHN Reference Number: R20181204) in keeping with requirements of the National Health and Medical Research Council (NHMRC) National Statement on Ethical Conduct in Human Research 2007 incorporating all updates.