Patient population and selection
This study is a retrospective analysis in our institute (Changhua Christian Hospital, Changhua, Taiwan). All patients over 18 years of age undergoing segmentectomy from January 2017 to September 2020 were included in the study. Patients without NSCLC or with positive lymph node invasion were excluded. Other exclusion criteria were the tumor being larger than 20 mm in diameter and missing pulmonary function data.
Our study was approved by the institutional review board in our institution (IRB-201004), and informed consent from all participants was waived. We analyzed the age, gender, tumor location, forced expiratory volume in one second (FEV1), tumor differentiation, tumor histology, pathologic T stage, tumor subtype, spread through air spaces (STAS), pleural invasion and lymphovascular invasion. We classified histologic subtypes as adenocarcinoma, squamous cell carcinoma, and other histologic types. Patients were divided into two groups: group A (received iVATS extended segmentectomy) and group B (received traditional segmentectomy). The decision to perform iVATS extended segmentectomy or traditional segmentectomy was made by surgeon’s preference. If the nodule was located at intersegmental area and hard to make enough resection margin, iVATS extended segmentectomy would be preferred. Otherwise, traditional segmentectomy would be performed if the nodule was in the central of segment.
The outcome measures for our study were the closest margin to a staple line, the margin/tumor diameter ratio (M/T ratio) and the enough margin rate. The chosen classification of margin was deflated lung margin based on the pathology reported by a qualified pathologist. The definition of enough margin was based on National Comprehensive Cancer Network (NCCN) practice guidelines, which described “sublobar resection should achieve parenchymal resection margins ≧ 2cm or ≧ the size of the nodule.” (5) Every observation was staged according to the eighth edition of the TNM staging system, published in 2017.
The iVATS segmentectomy procedure:
Under general anesthesia, patients were positioned in the lateral decubitus position in a hybrid operating room. All lines and tubes were secured and taped. We used robotic C-arm cone beam CT (Artis Pheno; Siemens Healthcare GmbH, Forchheim, Germany) for the scanning. A test-C-arm-movement was performed to ensure the scanner would not collide with the patient before the scanning. The whole scan was performed with breath hold at end inspiration by clamping the endotracheal tube.
We measured the insertion point at axial view and laid out the needle path under the syngo Needle Guidance of a syngo X-Workplace with a three-dimensional view. The guidance needle was inserted to around a 10mm depth in the pleura toward the nodule. A cross laser beam for incision location projected onto the patient’s skin. We punctured an 18-gauge marker needle into the thorax with the cross-laser guidance after holding. After another scan for confirmation of the appropriate needle location, diluted methylene blue dye (0.15ml) plus normal saline (0.25ml) were injected. The purpose of this mixture was for the methylene blue dye to be seen within 5 millimeters of the surface without coloring the nodule. The operation started after sterilization and one lung ventilation.
We performed extended segmentectomy with single-incision VATS. Most of the methylene blue dye could be seen clearly on the surface of the lung. After the division of the segmental bronchus, we identified the inflation-deflation line and the nodule site. A safe margin of 2 centimeters away from the nodule site was created and divided with a linear stapler (Figure 1).
On the other hand, we performed traditional segmentectomy while the nodule was clearly away from inter-segmental area. Pre-operative CT-guided micro-coil localization would be done one day before the operation in order to help finding the nodule intra-operatively. We also use the inflation-deflation method to identify the inter-segmental plane.
We routinely check resection margin immediately on a back table. We make sure the free margin and measure the resection margin on every pathology. If the margin is less than 5mm, we would perform additional wedge resection.
Statistical Analyses
The following clinic-pathologic factors were included into analyses: age, gender, tumor location, FEV1, tumor differentiation, tumor histology, pathologic T stage, tumor subtype, STAS, pleural invasion and lymphovascular invasion. Since most of the continuous variables in this study did not follow the normal distribution, we used the Mann-Whitney U Test to compare the median and the inner interquartile range (IQR) between the two groups. As for the categorical variables, we used the Chi-Squared Test or Fisher's Exact Test to compare the number and proportion between the two groups. The linear regression model was used to determine the effects of surgical methods on resection margin. Univariable and multivariable analyses were performed. The variables that were significantly different between the two groups, as well as the variables that were associated with the resection margin, were selected into the maximum model. They were controlled and adjusted together to eliminate the effects of confounders. We used the coefficient p-values to decide whether to include variables in the final model. If there is a variable with a p-value greater than 0.05 in the multiple linear regression mode, it will be removed, and the variables that are still statistically significant are retained as the final mode.
All calculations were performed using the IBM SPSS Statistics for Windows, Version 22.0 (IBM Corp., Armonk, NY). Statistical analysis with a p value less than 0.05 was considered statistically significant.