Effects of da Vinci robot versus thoracoscopic surgery on body trauma and lymphocyte subsets in lung cancer patients: A propensity score matching study

To assess the impact of da Vinci robot versus thoracoscopic surgery on body trauma and lymphocyte subsets in lung cancer patients.


| INTRODUCTION
Lung cancer is one of the most common malignancies worldwide and the leading cause of tumor-related deaths. 1 The gold standard of treatment for early-stage non-small cell lung cancer (NSCLC) is surgical resection. 2,3 Video-assisted thoracoscopic surgery (VATS) offers less pain, shorter hospital stay, and fewer perioperative complications than conventional thoracotomy, and is no less effective than thoracotomy in terms of long-term oncologic outcomes. 4 In addition, previous studies have shown that VATS is associated with the release of fewer inflammatory cytokines, which may be an important cause for the superiority of minimally invasive thoracic surgery over open thoracic surgery. 5 The application of VATS in lung cancer surgery is well established, but VATS has some shortcomings: long learning curve, counterintuitive operation logic, lack of stereoscopic view, and poor instrument mobility, and so forth.
However, the application of robot-assisted thoracoscopic surgery (RATS) can effectively solve the above-mentioned issues. 6,7 In comparison with VATS, whether RATS is of lower body trauma and immune suppression remains unknown. Therefore, this study

| RATS group
The patient was intubated with a double lumen endotracheal tube, under intravenous inhalation balanced with general anesthesia, and the healthy side was ventilated with one lung, in the healthy side position, with the chest padded and both upper extremities flexed in the with a pillow between arms position to lower the shoulder and hip to avoid mechanical compression. The da Vinci robot is loaded and punched using the three-arm, four-hole method (Si system). The left-hand instrument is an atraumatic grasping forceps and the righthand instrument is a monopolar electrocoagulation hook. A manually introduced stapler is also required. The lateral anterior approach 3-4-6-8/9 port strategy was used, that is, the mirror hole was placed at the sixth intercostal space in the posterior axillary line, the remaining two operating holes were placed at the eighth/ninth intercostal space

| VATS group
Generally, a 1.2 cm incision in the seventh or eighth intercostal space in the midaxillary line is used as the access hole, and a 3 cm incision in F I G U R E 1 Intraoperative lymph node dissection (robotic-assisted thoracic surgery). the fourth or fifth intercostal space in the anterior axillary line is used as the operating hole.

| Detection of inflammatory markers and lymphocyte subsets
Blood samples of patients were collected at four time points: venous blood of upper limbs was collected on an empty stomach 1 day before the operation and 1, 3, and 5 days after the operation.
Patients were tested for inflammatory markers (CRP, IL-6) and lymphocyte subsets (CD 3+ , CD4 + , CD8 + , and CD4 + /CD8 + ), and all blood samples were done by the same technicians in the laboratory department of our center.  and TNM stage. Continuous variables were expressed as mean ± SD (x ± s), and two independent samples t-test was used for comparison between groups. Categorical variables were expressed as frequencies and percentages (%), and group comparisons were made using the chi-square test or Fisher test. p < 0.05 was considered to be a statistically significant difference.

| Propensity score matching
The differences in age and tumor site between the two groups of patients before PSM were statistically significant. Sex, age, BMI, smoking history, underlying disease, tumor size, surgical procedure, tumor site, pathological type, T stage, N stage, and TNM stage factors were included in PSM, and 138 patients in the RATS group and 138 patients in the VATS group were successfully fitted after 1:1 matching, and none of the differences in confounding variables were statistically significant; see Table 1.

| Surgical results
The surgical data of the two groups of patients after PSM are specified in Table 2 Table 2.

| Comparison of inflammatory markers and lymphatic subgroup indicators
The postoperative CRP and IL-6 indexes in both RATS and VATS groups were higher than those before surgery, and the increase in CRP and IL-6 indexes in the RATS group was smaller than that in the VATS group on postoperative Days 1, 3, and 5, the difference was statistically significant; see Table 3.
The differences in peripheral blood T lymphocyte subsets between the two groups were not statistically significant before surgery, and the levels of T lymphocyte subsets were lower after surgery than before surgery in both groups. On postoperative Days 1 and 3, peripheral blood CD3 + , CD4 + , CD8 + T lymphocyte levels, CD4 + /CD8 + , and total lymphocyte counts were significantly lower in the VATS group compared with the RATS group. On postoperative Day 5, peripheral blood CD3 + and CD4 + T lymphocyte levels were significantly lower in the VATS group compared with the RATS group; CD8 + T lymphocyte levels, CD4 + /CD8 + , and total lymphocytes were F I G U R E 2 Intraoperative lymph node dissection (robotic-assisted thoracic surgery).
T A B L E 1 Comparison of baseline information before and after propensity score matching between the two groups (cases (%)/x ± s). lower, but the differences were not statistically significant; see Table 3. In this study, we found that the RATS group has a shorter operative time than that in the VATS group, indicating that RATS has some advantages in shortening the operative time and thus could reduce the impact on the function of the patient's organism.

| DISCUSSION
Our present study showed that RATS can reduce intraoperative surgery and is more conducive to immune recovery after surgery. [10][11][12] In this study, by comparing the peripheral blood T lymphocyte subsets before and after surgery, it was found that RATS was less destructive to patients' cellular immune function than VATS, and patients with RATS recovered cellular immunity more quickly after surgery, fully reflecting the advantages of robotic surgery treatment. However, even for patients treated with RATS, surgical trauma inevitably causes damage to the immune function of the body. The levels of T lymphocytes in T A B L E 2 Surgical data of patients (cases (%)/x ± s). and CRP and IL-6 are inflammatory markers commonly used in clinical practice to assess surgical trauma. 14,15 Our study showed that the increase in CRP was less in the RATS group than that in the VATS group on postoperative Days 1, 3, and 5. The postoperative IL-6 level was significantly higher in the VATS group than that in the RATS group, which also proved that IL-6 could reflect the degree of trauma more sensitively, and the effect of RATS surgery on IL-6 in patients was smaller. This suggests that RATS is less traumatic to the body and causes a less severe inflammatory response, which may be related to the shorter procedure time, less bleeding, and less stressful reaction to RATS.
There are some limitations and shortcomings of our present study: first, the results may be biased because the data source included in the study was a single center and the sample size was relatively limited for a retrospective study; second, although VATS suppresses lymphocytes more severely in the early postoperative period, because of the short duration of the difference in postoperative lymphocyte subpopulation levels between the two groups, further studies are needed to determine whether this difference will have a long-term effect on the immune function of the patient's organism and whether it will affect the patient's long-term survival or play a role in tumor recurrence (data not yet available as our long-term follow-up is still ongoing).