Thoracoscopic Surgery Without Drainage Tube Placement for Peripheral Lung Nodules

Journal Pre-proof Thoracoscopic Surgery Without Drainage Tube Placement for Peripheral Lung Nodules Hsien-Chi Liao, MD, Shun-Mao Yang, MD, Ming-Hui Hung, MD, MS, Ya-Jung Cheng, MD, PhD, Hsao-Hsun Hsu, MD, PhD, Jin-Shing Chen, MD, PhD PII:

S0003-4975(19)31860-0

DOI:

https://doi.org/10.1016/j.athoracsur.2019.10.048

Reference:

ATS 33293

To appear in:

The Annals of Thoracic Surgery

Received Date: 14 May 2019 Revised Date:

9 October 2019

Accepted Date: 18 October 2019

Please cite this article as: Liao HC, Yang SM, Hung MH, Cheng YJ, Hsu HH, Chen JS, Thoracoscopic Surgery Without Drainage Tube Placement for Peripheral Lung Nodules, The Annals of Thoracic Surgery (2020), doi: https://doi.org/10.1016/j.athoracsur.2019.10.048. This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. © 2019 by The Society of Thoracic Surgeons

Thoracoscopic Surgery Without Drainage Tube Placement for Peripheral Lung Nodules Running Head: Drainless VATS for lung nodules

Hsien-Chi Liao, MD,1 Shun-Mao Yang, MD,2 Ming-Hui Hung, MD, MS, 3,4 Ya-Jung Cheng, MD, PhD,4 Hsao-Hsun Hsu, MD, PhD,5 and Jin-Shing Chen, MD, PhD5

Department of Traumatology1, Department of Anesthesiology4, and Division of Thoracic Surgery, Department of Surgery5, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan. Division of Thoracic Surgery, Department of Surgery2, and Department of Anesthesiology3, National Taiwan University Hospital Hsin-Chu Branch, Hsinchu City, Taiwan.

Article word count: 3245

Corresponding author: Hsao-Hsun Hsu, MD, PhD Division of Thoracic Surgery, Department of Surgery, National Taiwan University Hospital and National Taiwan University College of Medicine, No. 7, Zhongshan S. Rd., Zhongzheng Dist., Taipei City 100, Taiwan (R.O.C.) E-mail: [email protected]

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ABSTRACT Background: Although drainage tube placement following thoracoscopic pulmonary resection is considered mandatory, the drainless approach after pulmonary resections may be feasible in selected patients. We aimed to determine whether a drainless approach is safe and associated with shorter hospital stay after thoracoscopic surgery for peripheral lung nodules. Methods: This single-center, open-label, parallel-group, prospective, randomized, controlled trial enrolled patients with peripheral lung nodules treated via uniportal thoracoscopic wedge resection. After confirming the absence of air leaks and before closing the wound, patients were allocated to receive or not receive drainage using a chest tube, according to a pre-established randomization sequenced provided in sealed envelopes. The primary endpoint was the length of postoperative hospital stay. Results: Of 107 patients who agreed to participate in the study between August 2016 and September 2017, 100 were randomized to the drainage group (n=50) or drainless group (n=50) for intention-to-treat analysis. Patients in the drainless group had shorter postoperative hospital stay (mean, 1.2 vs 2.6 days, P<0.001), shorter surgery duration (mean, 59.0 vs 73.7 minutes, P=0.001), and lower pain on postoperative day 1 (mean, 0.9 vs 1.2 points, P=0.011). In the drainless group, residual pneumothorax was noted in 31 (62%) patients at 6 hours, in 18 (36%) patients at 1 day, and in one (2%) patient at 10–14 days postoperatively. Medical costs were also significantly lower in the drainless group. Conclusions: Uniportal thoracoscopic wedge resection without drainage is feasible and safe for selected patients with peripheral lung nodules.

Abstract words count: 243

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Abbreviations and Acronyms VATS = video-assisted thoracoscopic surgery POHS = postoperative hospital stay CT = computed tomography POD = postoperative day VAS = visual analogue scale CxR = chest radiographs BMI = body mass index FVC = forced vital capacity FEV1.0 = forced expiratory volume in 1 second NA = not applicable TWD = New Taiwan dollar

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Placement of a drainage tube (such as a chest tube or pigtail catheter) following thoracic surgery has been the gold standard approach for draining residual blood, pleural effusions, or pneumothorax(1, 2). However, the drainage tube is often reported as the main cause of postoperative pain(3-5) and interferes with the patient’s active movements(6), thus prolonging the duration of hospitalization and increasing medical costs(7). Several retrospective studies found that omission of chest tube placement after various thoracoscopic procedures is a safe and feasible approach that may help reduce postoperative pain and shorten the hospital stay(3, 7-9). Without drain placement following pulmonary resection by video-assisted thoracoscopic surgery (VATS), however, the risk of symptomatic pneumothorax or pleural effusions requiring further reintervention remains unclear(10, 11). We performed a prospective, randomized trial comparing the drainage and no-drainage (drainless) strategies of thoracoscopic surgery for resection of small peripheral lung nodules, aiming to investigate whether the drainless approach represents a safe and cost-effective treatment option.

Material and Methods Study design and settings We conducted a single-center, prospective, open-label, parallel-group, randomized, controlled trial enrolling patients with small peripheral lung nodules requiring wedge resection via VATS between August 2016 and September 2017. At the end of surgery and upon confirming the absence of air leaks, the patients were allocated to receive chest drainage using a chest tube (drainage group) or to not receive drainage (drainless group), according to a randomization sequence received in sealed envelopes. The primary endpoint was the duration of the postoperative hospital stay (POHS). The secondary endpoints were surgery duration, postoperative pain, incidence of adverse events, degree of residual neuralgia and wound satisfaction at 1 month, and medical costs. The study protocol was approved by our hospital’s institutional review board. Written informed consent was obtained from all patients. This trial was registered at http://www.clinicaltrials.gov (trial registration ID: NCT02817048).

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Participants The study population comprised patients aged 20–80 years indicated for thoracoscopic wedge resection of a peripheral lung nodule located within 2 cm of the visceral pleura and having a diameter <2 cm, as determined on chest computed tomography (CT). The following exclusion criteria were applied: moderate-to-severe obstructive or restrictive pulmonary diseases (GOLD guidelines: presence of post-bronchodilator forced expiratory volume in one second (FEV1) < 80% in combination with a FEV1/forced vital capacity (FVC) < 70%); anatomical resection such as lobectomy or segmentectomy; multiple wedge resections; air leaks following pulmonary resection; previous ipsilateral thoracic operation; pregnancy or lactation; other serious concomitant illnesses or medical conditions such as congestive heart failure, bleeding tendency, liver cirrhosis, chronic renal disease, a condition requiring long-term use of anticoagulants or steroids, or active infection requiring intravenous antibiotics.

Randomization and masking Patients were randomized with a 1:1 ratio according to a computer-generated sequence of random numbers listed in sequentially numbered, sealed envelopes kept by a study nurse blinded to the study data. On the day of the operation, following thoracoscopic surgery and confirmation of the absence of air leaks, the envelope was opened by the study nurse to determine whether a chest tube would be placed for drainage or not.

Uniportal thoracoscopic procedures The techniques used for uniportal thoracoscopic wedge resection, mediastinal lymph node sampling, and detection of air leaks are described in detail elsewhere(3, 12). Briefly, under general anesthesia and intubation using a double-lumen endotracheal tube or a single-lumen tube with a blocker, the patients were placed in the lateral decubitus position and the ipsilateral lung was deflated. A 5-mm 30° thoracoscope was inserted through a 3-cm incision at the level of the fifth or sixth intercostal space in the middle axillary line. Through this single incision, the location of the lung nodules was

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confirmed by finger palpation, using endoscopic instruments, or by Patent Blue V dye localization (Guerbet, Aulnay-sous-Bois, France) conducted using preoperative-CT guidance(13). Thoracoscopic wedge resection of the affected lung tissue was performed using an articulating endoscopic linear cutter with 3.0 or 4.5-cm blue or green cartridges (Covidien, Dublin, Ireland; or Ethicon Endo-Surgery, Cincinnati, OH, USA)(14, 15). The resected lung tumor was sent for frozen-section examination. If the pathology examination revealed primary or metastatic lung cancer, further lung resection was performed to achieve a safety margin of >2 cm. Lymphadenectomy was performed via lymph node sampling rather than radical dissection.

Air-leak testing and placement of the chest tube for drainage At the end of the surgical procedure and before randomization, the treated lung was examined for air leaks by two air-leak tests (Figure 1). First, an ordinary underwater air-tightness test was conducted by gradually inflating the operated lung(11). The lung was immersed in saline, and manually-assisted ventilation was applied until the lobe with the lesion expanded to its full volume(16). Second, an additional check for air leaks was conducted using a tube (CV-1107 silicone CWV drain, 7 mm; Besmed Health Business Corporation, New Taipei, Taiwan) connected to a vacuum ball (CW-1S150 CWV reservoir, 150 mL; Besmed Health Business Corporation) (Figures 2A and 2B). The drainage tube was connected to a vacuum ball outside the thoracic cavity, and the CWV catheter was placed next to the staple line to remove residual air and pleural effusion before wound closure. Patients demonstrating any air leakage during these two air-tightness tests were excluded from randomization. After confirming that there was no air leakage from the treated lung, patients were assigned to either the drainless or drainage group, according to the contents of the sealed envelope. For patients allocated to the drainless group, the uniportal incision was immediately closed using continuous sutures after removing the CWV drain tube. For patients in the drainage group, a 20, 24, or 28-F chest tube was inserted through the uniportal incision and fixed in place after removing the CWV drain tube. The wound was then closed layer by layer.

Postoperative monitoring and care

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Postoperatively, all patients were extubated in the operating theatre and managed according to the same protocol. Postoperative analgesics included routine oral nonsteroidal analgesics and acetaminophen. On postoperative day (POD) 1 and 2, the intensity of postoperative pain was evaluated using a visual analogue scale (VAS) where 0 represented no pain and 10 represented intolerable pain. Intramuscular meperidine hydrochloride (50 mg) was administered every 4–6 hours if pain was intolerable or intractable using oral analgesics (VAS score >7)(5, 17). In the drainless group, chest radiographs (CxR) were performed at 4–6 hours and on the morning after surgery. The size of residual pneumothorax was defined as the largest distance between the pleural line and the chest wall on CxR. Patients were eligible for discharge if no significant pneumothorax (<5 cm in diameter) was noted on serial CxR. A chest tube would be inserted or needle aspiration would be performed if CxR revealed significant pneumothorax (>5 cm in diameter) or progress of the residual pneumothorax, or if the patient’s respiratory status deteriorated clinically. In the drainage group, CxR was performed only on POD 1. If no air leak was present and the daily drainage amount was less than 200 mL, the chest tube was removed. All patients were monitored at the outpatient department at 10–14 days, 1 month, and 6 months after the operation, with CxR and clinical examination routinely performed during the follow-up visits. Any complications after the operation were recorded. Prolonged tube drainage was defined as the need to retain the tube for longer than 3 days. Subcutaneous emphysema was defined as the presence of subcutaneous air on CxR. Residual pleural effusions were defined as blunting of the costophrenic angle in the ipsilateral lung on CxR. Follow-up was also conducted by a registered nurse blinded to group allocation, who used a standardized questionnaire for evaluating residual postoperative neuralgia and wound satisfaction at 1 month after the operation. Residual neuralgia was evaluated using a scale from 0 to 5, where 0 corresponded to no pain, 1 to occasional discomfort, 2 to occasional pain requiring use of analgesics, 3 to pain requiring use of non-opiate analgesics, 4 to regular pain requiring use of opiates, and 5 to severe and intractable pain. The patients were also asked to score their satisfaction with the scar on a scale from 1 (very dissatisfied) to 5 (very satisfied). A flow diagram of clinical trial enrolment, randomization, follow-up, and data analysis is provided in Figure 3.

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Statistical analysis Intention-to-treat analyses (all randomly assigned patients) were used for the primary and secondary endpoints. Continuous variables were expressed as means ± standard deviations and compared using t-tests. Categorical variables were expressed as percentages and compared using Pearson chi-square tests. Statistical analyses were performed using SAS version 21 (IBM, Armonk, NY, USA). P-values < 0.05 were considered to indicate statistical significance.

Sample size estimation The primary endpoint was the length of POHS. According to previous research, the duration of POHS was shorter in the drainless group than in the chest tube group (3.1±0.7 vs 4.4±1.3 days, P=0.012)(3). Therefore, we assumed that the POHS would be approximately 3.1 days for the drainless group and 4.4 days for the control group. To detect a meaningful effect in the main outcome variable with a power of 0.8 and significance level of 0.05, the minimum sample size for a randomized study was calculated that at 78 patients (39 in each group). Considering a drop-out rate of 30%, we initially aimed to enroll 101 patients.

Results Over the course of 14 months, 107 patients with small peripheral lung nodules were enrolled (Figure 3). Seven patients were excluded due to air leaks noted immediately after thoracoscopic wedge resection. Five patients failed the underwater air-tightness test, and the remaining 2 patients failed the vacuum ball air-leak test. They were all excluded from randomization. The remaining 100 patients were randomly assigned to either the drainless (n=50) or drainage group (n=50). The demographic data and baseline characteristics are summarized in Table 1. The two groups did not differ in terms of age, sex, height, weight, body mass index, smoking status, pulmonary function, nodule size, nodule depth, nodule location, malignancy rate, or prevalence of comorbidities.

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The operative characteristics are summarized in Table 2. Surgery duration was shorter in the drainless group than in the drainage group (59.0±15.8 vs 73.7±26.6 minutes, P=0.001). The two groups were comparable in terms of the rates of preoperative dye localization, the length and width of the resected lung tissue, and the rates of additional lymphadenectomy. The postoperative outcomes are summarized in Table 3. Subcutaneous emphysema was noted in 11 patients (11/50, 22%) from the drainless group and in 6 patients (6/50, 12%) from the drainage group. In the drainless group, only 2 (2/50, 4%) patients required simple needle aspiration on POD 1 because of large pneumothorax, and none required chest tube insertion or reoperation. Compared to the patients in the drainage group, those in the drainless group had shorter POHS (mean, 1.2 vs 2.6 days, P<0.001) and lower pain scores on POD 1 (mean, 0.9 vs 1.3, P=0.011). Total treatment costs were smaller in the drainless group than in the drainage group (mean, 139084.9 vs 157655.5 TWD, P<0.001). No patient (in either group) required readmission after discharge. At 1 month postoperatively, residual neuralgia and wound satisfaction were comparable between the two groups. The postoperative radiographic findings are summarized in Table 4. In the drainless group, residual pneumothorax was noted in 31 (31/50, 62%) patients at 4–6 hours, the mean and standard deviation for the sizes of pneumothorax were 0.87 ± 0.65 cm. The rate of residual pneumothorax was significantly higher in the drainless group on POD 1 (18/50, 36% vs 5/50, 10%; P=0.002), and the mean and standard deviation for the sizes of pneumothorax were 1.67 ± 1.31 cm. It had become

comparable between the groups by the time of the first outpatient follow-up visit (1/50, 2% vs 1/50, 2%; P=1.000). The rate of residual pleural effusions was comparable between the groups. At 1 month postoperatively, CxR revealed no residual pneumothorax or pleural effusion in any patient.

Comment Our study is the first prospective, randomized, controlled trial to investigate whether uniportal thoracoscopic wedge resection without drainage tube placement is safe and cost-effective. Our findings indicate that, as long as all air leaks have been adequately handled before wound closure, drainless thoracoscopic surgery for peripheral lung nodules is safe. Moreover, patients who do not

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receive a chest tube have shorter hospital stay, less postoperative pain, and lower treatment costs compared to those noted among patients who do receive a chest tube for drainage. The mean duration of postoperative hospitalization was 1.2 days in the drainless group and 2.6 days in the drainage group, indicating that many patients who did not receive a chest tube were discharged the day following surgery, and suggesting that residual pneumothorax of ≤5 cm at this time does not generally represent cause for concern. Indeed, most pneumothoraces had resolved completely at the first outpatient follow-up visit. These findings implied that drainless uniportal VATS for pulmonary wedge resection can be conducted as an outpatient procedure(3). Previous research reported that male sex and compromised pulmonary function are risk factors for postoperative air leakage and need for chest tube drainage(15, 18). Therefore, we employed two air-leak tests, including the traditional water-seal leakage test and an additional test involving a vacuum ball combined with a CWV drain. Furthermore, due to safety and ethics concerns, patients with moderate or severe ventilatory defects were not enrolled in this pilot study. In this study, the majority (87/100) of participants were female and the proportion of never-smokers was very high (96/100). The reason for these unique characteristics of the study population may be multifactorial. Although smoking is recognized to account for 85%–90% of lung cancer cases in Western countries, in a worldwide context and especially in East Asia, 25% of patients with lung cancer are non-smokers(19-21). In Taiwan, the incidence of newly diagnosed lung cancer, has increased steadily over time, especially in the non-smoking female population (22, 23). This suggests that low-dose chest CT screening for early detection of small lung nodules is indicated more often in non-smoking Taiwanese, even in the absence of symptoms. The concerns associated with omitting chest tube drainage after pulmonary resection refer to the risk of symptomatic pneumothorax, bleeding, and pleural effusions. In this study, we selected patients with peripheral lung nodules but normal pulmonary function, who had been indicated for wedge resection; our choice of study population was based on the fact that the risk of large pneumothorax, symptomatic bleeding, and effusions is low in patients with normal pulmonary function. Even though 62% of patients in the drainless group had residual pneumothorax at 4–6 hours postoperatively, only two patients required reintervention and both were successfully treated via simple needle aspiration.

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Although the rate of residual pneumothorax on POD 1 was higher in the drainless group than in the drainage group, there was no difference between the groups by the time of the first follow-up at the outpatient department. This observation suggests that residual air following surgery could be absorbed safely and quickly. Indeed, the rate of residual pleural effusion did not differ significantly between the groups. We found that pain scores on POD 1 were lower in the drainless group, whereas those on POD 2 were comparable between the groups. This phenomenon indicated that postoperative chest pain following VATS is caused mainly by chest tube placement(15, 24, 25). Thus, the pain scores became comparable between the two groups starting on POD 2 because most chest tubes were removed on POD 1. Although all our patients in this study were treated via uniportal thoracoscopic wedge resection, two patients expressed dissatisfaction after the surgery (Table 3). Both complained about post-operative chronic neuralgia over the chest wall, and were not satisfied with the effect of painkillers. Post-operative chronic neuralgia is one of the most common complications in thoracic surgery. In order to prevent this side effect, we are committed to technical improvements, such as decreasing the numbers of VATS ports, injecting intercostal nerve blockers intra-operatively, and attempting to remove the drainage tube earlier. We obtained better responses from most patients in the outpatient clinic with respect to wound healing and pain sensation. Despite this, a few patients suffered from post-operative chronic neuralgia. In our experience, most of the symptoms improve within 3~6 months under medical control, and only less than 10% of the patients had permanent neuralgia due to intercostal nerve injury. Treatment cost was lower in the drainless group than in the drainage group, which can be explained from several perspectives. Specifically, patients who did not receive a chest tube had shorter POHS and required fewer procedures (e.g., chest tube and chest bottle were not required; wound care was easier)(6, 8, 26). In addition, the mean surgery duration was also shorter in the drainless group because of no need to insert a chest tube. We acknowledge several limitations of the study. First, this was an open-label trial following

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randomization (i.e., at the time of wound closure). Second, we only performed wedge resection using the uniportal VATS approach. Thus, it remains unclear whether our conclusions are applicable in patients requiring anatomical resection such as lobectomy or segmentectomy. Third, this study included a large proportion of never-smokers and female patients. A large-scale, prospective, multi-center, randomized controlled study should be conducted to clarify the impact of sex and smoking habits. In conclusion, our study brings clear evidence that drainless uniportal VATS can be performed safely and effectively in selected patients with peripheral lung nodules. The surgical strategy presented in our study could be considered as a less invasive and economically advantageous alternative to traditional thoracoscopic surgeries involving routine placement of a drainage tube postoperatively.

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Table 1. Patient Demographics and Baseline Characteristics Variablea

Drainless Group

Drainage group

(n=50)

(n=50)

Age, years

52.4±10.9

54.9±10.1

0.238

Female sex

44 (88)

43 (86)

0.766

Height, cm

159.2±6.8

160.2±7.7

0.504

Weight, kg

55.8±7.5

59.1±9.9

0.059

BMI, kg/m2

21.9±2.5

22.9±3.1

0.081

1 (2)

3 (6)

0.307

112.9±14.4

111.3±15.7

0.597

111.3±15.4

112.7±16.5

0.673

Nodule size, cm

0.7±0.3

0.8±0.3

0.361

Nodule depth, cm

0.6±0.7

0.7±0.8

0.408

Smoking FVC, % of

P-value

prediction FEV1.0, % of prediction

Affected lobe

0.131

Right upper

10 (20)

17 (34)

Right middle

3 (6)

8 (16)

Right lower

15 (30)

9 (18)

Left upper

15 (30)

9 (18)

16

Left lower Malignancy

7 (14)

7 (14)

32 (64)

38 (76)

Comorbidity

a

0.190 0.192

Hypertension

5 (10)

4 (8)

Diabetes mellitus

1 (2)

1 (2)

Cardiac diseases

1 (2)

8 (16)

Asthma

1 (2)

0

Continuous data are shown as mean ± standard deviation, while categoric data are shown as

frequency (percentage). BMI = body mass index; FVC = forced vital capacity; FEV1.0 = forced expiratory volume in 1 second.

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Table 2. Operative Results Variablea

Drainless group

Drainage group

(n=50)

(n=50)

59.0±15.8

73.7±26.6

0.001

36 (72)

39 (78)

0.488

Resected lung length, cm

5.5±1.8

6.2±2.4

0.129

Resected lung width, cm

2.8±0.7

3.0±1.1

0.261

Surgery duration, minutes Preoperative CT-guided dye

P-value

localization

Operative method

0.182

Wedge resection only

7 (14)

3 (6)

Wedge resection with

43 (86)

47 (94)

lymphadenectomy a

Continuous data are shown as mean ± standard deviation, while categoric data are shown as

frequency (percentage). CT = computed tomography.

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Table 3. Treatment Outcomes Variablea

Drainless group

Drainage group

(n=50)

(n=50)

NA

2 (4)

11 (22)

6 (12)

P-value

Adverse events Prolonged tube drainage >3 days Subcutaneous emphysema Reintervention on POD 1b

2 (4)

0.183

0

Post-operative pain score POD 1

0.9±0.7

1.3±0.9

0.011

POD 2

0.5±0.6

0.9±1.6

0.064

NA

1.2±0.7

1.2±0.5

2.6±0.9

<0.001

139084.9±17776.1

157655.5±24495.4

<0.001

0

0

Duration of postoperative chest drainage, days Duration of postoperative hospital stay, days Treatment cost, TWD Readmission Residual neuralgia at 1 month

0.627

Pain score 0

20 (40)

20 (40)

Pain score 1

15 (30)

12 (24)

Pain score 2–3

10 (20)

12 (24)

Pain score 4

4 (8)

4 (8)

Pain score 5

1 (2)

1 (2)

Wound satisfaction at 1 month

0.082

Very satisfied

37 (74)

43 (86)

Satisfied

5 (10)

5 (10)

19

a

Acceptable

5 (10)

1 (2)

Dissatisfied

1 (2)

1 (2)

Very dissatisfied

2 (4)

0

Continuous data are shown as mean ± standard deviation, while categoric data are shown as

frequency (percentage). b

Simple needle aspiration for large pneumothorax

NA = not applicable; POD = postoperative day; TWD = New Taiwan dollar.

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Table 4. Radiographic Findings Variablea

Drainless group

Drainage group

P-value

(n=50)

(n=50)

At 4–6 hours

31 (62)

NA

On POD 1

18 (36)

5 (10)

0.002

1 (2)

1 (2)

1.000

0

0

At 4–6 hours

4 (8)

NA

On POD 1

4 (8)

3 (6)

0.695

At 1st outpatient visit

1 (2)

3 (6)

0.307

0

0

Residual pneumothorax on postoperative CxR

At 1st outpatient visit At 1 month Residual pleural effusions on postoperative CxR

At 1 month a

Data are shown as frequency (percentage).

CxR = chest radiography; NA = not applicable; POD = postoperative day.

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FIGURE LEGENDS Figure 1. Strategy of intraoperative air-leak testing applied in this study. Figure 2. Representative intraoperative photographs taken during drainless uniportal thoracoscopic wedge resection for peripheral lung nodules. (A) A drainage tube with multiple side-holes (CV-1107 silicone CWV drain, 7 mm) was inserted into the pleural cavity after confirming the absence of air leaks via the water-seal leakage test. (B) The drainage tube was connected to a vacuum ball (CW-1S150 CWV reservoir, 150 mL) outside the thoracic cavity to remove residual air and pleural effusion before wound closure. The uniportal incision was closed using continuous suture to facilitate the vacuum deairing procedure. Figure 3. Flowchart of patient enrolment, randomization, follow-up, and data analysis. *Reintervention with simple needle aspiration for residual pneumothorax. CxR = chest radiography; POD = postoperative day.

22

Patients with peripheral lung nodules

VATS wedge resection Underwater air-tightness test to check air-leak

Air-leak (+)

excluded

Air-leak (-) CWV drainage tube test to check air-leak Air-leak (-)

Enrolled into this study

Air-leak (+) excluded

A

B

107 patients signed consent and underwent VATS wedge resection and air leak tests 7 patients excluded due to failed to pass the air leak tests 100 patients without air-leakage after pulmonary resection were randomized enrolled into 2 groups

50 patients without receiving drainage tube placement

50 patients received traditionally drainage tube placement

CxR within post-op 6 hours 2 residual pneumothorax required simple aspiration*

50 patients in intension-to-treat analysis （ Drainless group ）

50 patients in intension-to-treat analysis ( Drainage group )

CxR on POD 1 100 patients discharged and regularly followed up at outpatient department until 6 months postoperatively

*Reintervention with simple needle aspiration for residual pneumothorax.