Ethics statement and patients
All procedures were carried out in accordance with the principles of the Declaration of Helsinki. The study was approved by the Clinical Research Ethics Committee at the Fujian Provincial Hospital, Fujian Province, China (K2015-022-01, September 30, 2015). Informed consent was obtained from all patients included in this study.
Inclusion and exclusion criteria
Patients whose chest CT scans showed pulmonary GGNs and who underwent segmentectomy at Fujian Provincial Hospital between March 2016 and September 2018 were enrolled in this study. The inclusion criteria were a single lesion located in the lateral one-third of the lung parenchyma with a diameter ≤2 cm, and according to the indications for segmental resection in the National Comprehensive Cancer Network (NCCN) guidelines, an indication for uniportal video-assisted thoracoscopic segmentectomy. On the contrary, the exclusion criteria were central lesions with a tumour-to-intersegmental fissure distance <2 cm, multiple lesions, patients who do not meet the indications for segmental resection based on the NCCN guidelines, and general conditions that do not allow surgery or preoperative examinations suggesting distant metastasis (see study flow diagram).
General information
All patients admitted to the hospital for surgical treatment, excluding those with poor surgical tolerance, distant metastasis, stroke sequelae, severe lung ventilation dysfunction, and other conditions, routinely undergo pulmonary function tests, cardiac ultrasound, total abdominal colour Doppler ultrasound, cranial magnetic resonance imaging, and whole-body bone scanning. All patients who met the enrolment criteria were included and randomly classified into the experimental group A and control group B using the coin method. This implies that, after obtaining informed consent from each patient who met the admission criteria, a coin was tossed to determine group allocation – if “heads”, patients were assigned to the experimental group A and if “tails”, patients were assigned to the control group B. All patients were blinded to their group allocation.
In total, 101 individuals met the inclusion criteria. Among them, 4 patients refused to participate in the experiment, 2 patients were excluded due to poor physical condition, 1 patient cancelled the surgery unexpectedly, and after allocation, 5 patients were indicated to have benign lesion based on the frozen section examination. These 5 patients, therefore, exclusively underwent wedge resection. For the experimental group A, 3D chest CT reconstruction combined with the 3D printing technique was used in simulating a model to analyse the anatomical relationship and variations. For control group B, only a 3D CT scan was performed. In total, 89 patients were included in this study; 51 and 38 patients were assigned to the experimental group A [21 men and 30 women, aged 43-80 years, mean age 62 years; 17 patients were smokers (all men)] and control group B [14 men and 24 women, aged 40-81 years, mean age 61 years; 9 patients were smokers (all men)], respectively. No significant differences were observed in the general characteristics between the two groups (Table 1).
Table 1. Characteristics of the study cohort.
|
|
Experimental group A (n = 51)
|
Control group B (n = 38)
|
Total (n = 89)
|
T /X2 value
|
p value
|
Age [year, average age (± SD)]
|
60.73±5.643
|
61.61±6.445
|
61.10±5.979
|
-0.685
|
0.495
|
gender
|
|
|
|
|
|
Male [no. of cases (%)]
|
21 (41.2)
|
14 (36.8)
|
35 (39.3)
|
0.171
|
0.679
|
Female [no. of cases (%)]
|
30 (58.8)
|
24 (63.2)
|
54 (60.7)
|
History of smoking
|
|
|
|
|
|
Smoker [no. of cases (%)]
|
17 (33.3)
|
11 (28.9)
|
28 (31.5)
|
0.194
|
0.659
|
Non-smoker [no. of cases (%)]
|
34 (66.7)
|
27 (71.1)
|
61 (68.5)
|
Position (no. of cases, proportion %)
|
|
|
|
|
|
Left lung
|
18 (35.3)
|
13 (34.2)
|
31 (34.8)
|
0.011
|
0.915
|
Right lung
|
33 (64.7)
|
25 (65.8)
|
58 (65.2)
|
LS1+2
|
3 (5.9)
|
2 (5.3)
|
5 (5.6)
|
0.829
|
1.000
|
LS1+2+3
|
3 (5.9)
|
3 (7.9)
|
6 (6.7)
|
LS4+5
|
3 (5.9)
|
2 (5.3)
|
5 (5.6)
|
L3
|
2 (3.9)
|
1 (2.6)
|
3 (3.4)
|
L6
|
2 (3.9)
|
2 (5.3)
|
4 (4.5)
|
L basal segment
|
5 (9.8)
|
3 (7.9)
|
8 (9.0)
|
RS1
|
6 (11.8)
|
4 (10.5)
|
10 (11.2)
|
RS1+2
|
7 (13.7)
|
5 (13.2)
|
12 (13.5)
|
RS3
|
3 (5.9)
|
2 (5.3)
|
5 (5.6)
|
RS6
|
5 (9.8)
|
3 (7.9)
|
8 (9.0)
|
R basal segment
|
12 (23.5)
|
11 (28.9)
|
23 (25.8)
|
3D reconstruction and 3D printing
All patients in both groups underwent plain and enhanced chest CT scans for further diagnosis and to determine tumour location. Additionally, 3D reconstruction and 3D printing were performed for the experimental group to further locate the tumour, determine the anatomical relationship and any anatomical variations, and to simulate the operative process. The Siemens Sensation 64-slice CT scanner with 1.2-mm pitch and 1.0-mm scanning thickness was used in this study. The contrast agent iofol, manufactured by Jiangsu Hengrui Pharmaceutical Co. Ltd. (100 mL: 74.1 g Chinese medicine quasi-word H20143027), was intravenously administered to the elbow. The arterial and venous phase images were collected 25 and 55 seconds after the injection of the contrast agent, respectively. The IQQA®-Chest system was used to preserve the pulmonary artery, pulmonary vein, bronchus, tumours, hilum, and swollen lymph nodes and to reconstruct these structures with a 1.50-mm thickness. The pulmonary artery was red, the pulmonary vein was blue, and the bronchus was white. The 3D model was printed with Objet1000 Plus (STRATASYS Company). The physical printing ratio was 1:1, and the printing material was photosensitive resin (Figure 1).
Preoperative positioning
The “coordinate positioning method” was utilised for preoperative positioning. This method is widely used for mapping and determining object positions. Generally, to determine the position of a point, the number or angle should be identified. In the plane, two axes perpendicular to each other and having a common origin to form a plane rectangular coordinate system are identified, with the horizontal and vertical axes noted as such. This method was somewhat different when determining the location of the lesion in the experimental and control groups.
The horizontal axis data were derived from the measurement of the horizontal level of the lung lesion observed in the CT image. The ‘clock alignment method’ was adopted, assuming that the horizontal plane of the right chest was a clock and the lesion was the part indicated by the hour hand. Using the right upper lung lesion as an example (Figure 2A), the horizontal CT section (where the lesion was located) was selected, the right chest contour was regarded as the clock face, the midline of the clavicle was the 12 o'clock position, and the right midline was intended to be the 9 o'clock position (Figure 2B). According to the ‘clock positioning method’, the lesion was at 7.5 points. In both groups, the horizontal axis clock positioning method can be established in the CT horizontal plane.
On the contrary, the measurement of the vertical axis adopted a ‘scale-localisation algorithm’. A difference was observed in the proportional positioning method between the experimental and control groups. In the experimental group, the upper end to the lower end of the lobe where the lesion was located on each longitudinal axis was considered as the measurement interval. Depending on the lobes, the upper end can be the tip of the lung or the interlobular fissure, whereas the lower end can be the interlobular fissure or the base of the lung. On the 3D lung model, the distance from the lesion to the upper and lower ends was measured on the vertical axis, and the proportional position of the lesion on the vertical axis was calculated. Furthermore (with the right upper lung lesion as an example), the axis on the 7.5-hour position on the 3D lung model was selected. The length of the lesion to the tip of the lung and the interlobular fissure was recorded as ‘a’ and ‘b’, respectively. The proportional position of the lesion on the vertical axis was calculated using the formula: [a/(a+b)] (Figure 2C).
In the experimental group A, the vertical position was located using the proportional segmentation method with the scale positioning technique, which was performed on the 3D lung model. The following steps were performed: (1) locate the lobe where the nodule was located on the 3D model; (2) measure the distance between the nodule and the upper boundary of the lobe (a) and the length of the upper and lower boundaries of the lobe (a+b); (3) the ratio of the distance from the upper boundary (a) to the length (a+b) of the upper and lower boundaries of the lung lobe [a/(a+b)] was the position of the nodule in the longitudinal axis of the lobe.
In the control group B, preoperative vertical positional localisation was performed according to the sagittal and coronal planes of the CT image, using the following steps: (1) identify the lobe where the nodule was located on the CT image; (2) count the number of CT slices of the nodule from the border of the lung (n) and the total number of CT layers (N) of the upper and lower boundaries of the lobe; (3) calculate the ratio of the number of CT layers (n) of the nodule to the upper boundary of the lobe to the total number of CT layers (N) of the upper and lower boundaries of the lobe, thereby positioning the nodule longitudinally in the lobe.
In addition to the coordinate localisation method, we similarly selected anatomical landmarks, such as the apex of the lung, bottom of the lung, front edge of the lung rib, midline of the lung rib surface, posterior edge line of the lung rib surface, and the interlobular fissure as references. Maneuverer, the lung segment area, tracheal block expansion, and methods of finger touch detection, among others, were performed to accurately position the lesion.
Surgical methods
All patients underwent uniportal video-assisted thoracoscopic segmentectomy and systemic lymphadenectomy. The operation was performed by the treatment team led by the chief physician of the Department of Thoracic Surgery, Fujian Provincial Hospital. The assistant adopted a “same side, high position, single hand, sideway” posture mirror6, and the operator performed the procedure using a thoracoscopic instrument. The location of the intraoperative nodules was determined using data from the preoperative positioning methods described previously. A wedge-shaped resection was initially performed and followed by an intraoperative frozen section examination. Based on the frozen section examination, the segmental vein, artery, and bronchus were separated at the anatomical level and the linear cutting suture device was broken or disconnected. To determine the inter-segment plane, the ‘Lung Expansion-Falling Method’7 was utilised for the last segment of the lung fissure. The two groups were separated from the inter-segment plane of the rib surface, and a straight-section cutting stapler was used to process the inter-segment plane. During the operation, the frozen tumour and margin tissues were sent for pathological examinations and the combined lung segment or lobectomy was determined according to the distance between the tumour and the margin (2 cm). Subsequently, a conventional systemic lymph node dissection was performed. One chest tube was placed in the posterior margin of the incision, and one micro-thoracic tube was placed in the lower thoracic cavity (Figure 3).
Observation indicators
Both procedures were performed by the same surgeon. The operation was performed by the chief physician and assisted by two surgeons. The perioperative condition of patients was monitored by the observer. This is a single-blind study. In other words, only the patients in this study were unaware of their group allocation.
The surgical method transfer rate, operative time, intraoperative blood loss, postoperative complication rate, and segmental conversion rate of the lobectomy were measured and all these variables, except the postoperative complication rate, constituted the primary outcome measures. We also evaluated differences in the aforementioned variables between the control and experimental groups. The surgical transfer rate refers to the proportion of cases converted to open surgery due to selective reasons such as intraoperative thoracic adhesions and intraoperative bleeding. The surgical method conversion rate is the proportion of cases in which segmental resection was converted to a lobectomy due to various factors during the operation. The operative time was defined as the time from the commencement of the skin incision to the completion of suturing (h). Intraoperative blood loss was defined as the amount of blood absorbed by the gauze and the intraoperative suction (mL). In addition, it was determined using the weighing method to calculate the attracting liquid haemoglobin content.
Statistical analysis
All data were analysed using SPSS21.0 statistical software. Measurement data were expressed as , and the two-sample t-test was used for comparison between groups. The number of count data (n), and the ratio of count data (%), calculated by the X2 test or Fisher’s exact probability method, were used in this study. P<0.05 indicated a statistically significant difference.