Minimally Invasive Surgery Versus Open Surgery for the Treatment of Rectal Gastrointestinal Stromal Tumor: A Propensity Score Matching Analysis of Short- and Long-Term Outcomes

Backgrounds Methods Selection bias was eliminated using the Results


Introduction
Gastrointestinal stromal tumors (GISTs) are the most common primary mesenchymal tumors in the gastrointestinal tracts, with an annual incidence of 7 to 15 per million population per year [1]. GISTs are believed to have originated from mesenchymal cells (Interstitial cells of Cajal) of the GI tracts. Besides, GISTs can occur throughout the gastrointestinal tract, most frequently in the stomach (51%) and small intestine (36%), rarely occur in rectum (5%) [2]. However, the latter in general have a higher degree of malignancy and poorer prognosis [3].
Surgical resection is the potential curative treatment for the localized GIST. Due to the rare incidence of lymph node metastasis, therefore the routine lymphadenectomy is not indicated in adults. Besides, ESMO guidelines and NCCN guidelines have shown that wide margins of tumor resection have not improved the outcomes, so the main recommended goal of resecting GISTs is to achevie both grossly and macroscopic negative margins(R0) [4,5], in addition, tumor rupture should be carefully avoid, which is directlly associated with the prognosis [6].
Recently, minimally invasive surgery have been explored for surgeons in treatment of several gastrointestinal tumors, including the rectal cancer. That proven technique is associated with less invasive trauma, shorter recovery times and length of hospital stays, but with no difference in oncological outcomes and survival [7,8], those studies indicate that minimally invasive surgery is feasible and safe to cure the rectal lesions. However, limited studies addressing the minimally invasive surgery for rectal GIST, and the clinical effeciancy about the minimally invasive surgery versus open surgery is not well established. In this study, we aimed to characterize the short-term and long term oncological outcomes among rectal GIST patients conducting minimally invasive surgery versus open surgery.

Patient selection
Rectal GIST patients were retrospective from January 2010 to December 2019 at Xiangya hospital Central South University. Patients who were assessed as resectable rectal GISTs by at least two experiment surgeons and underwent surgical resection of a primary rectal GIST were included (Fig. 1), and then patients were divided into two groups: whose who underwent open surgery (OPEN) and those who underwent minimally invasive surgery (MIS)(including transanal resection, transanal minimally invasive surgery, transanal endoscopic microsurgery and laparoscopy

Data collection
The demographic and clinicopathologic data were supplemented by our clinic and pathologic system, Follow-up data were collected by our clinic system and connection to the patients, and the last follow-up was conducted in October 2019 or prior to patient death for any cause.

Propensity Score Matching (PSM)
For all the patients, six covariates (age, gender, body mass index, clinical symptom, tumor size, tumor distance above the anal edge) that might affected the surgery methods of patients were selected to calculated the propensity score. Then, a subset analysis of open surgery and minimally invasive surgery was conducted to evalutate the short-and long-term outcomes.

statistical analyses
The counting data are shown as percentages, and measurement data are shown as the mean or median with standard deviation (SD). Patient characteristics between each group were compared by chi-square test and Student's t test or one-way ANOVA was used for comparison between different groups. The progression free survival (PFS) and overall survival(OS)was obtained by the Kaplan-Meier method and differences between Kaplan-Meier curves were investigated by the log-rank test. Statistical analysis was performed using SPSS V26.0 (SPSS Inc. USA). A value of P was considered to be statistically signi cant below the 5% level.

Results
Demographic data and clinicopathologic data A total of 32 patients with primary rectal GIST who underwent surgery were eligible during January 2010 to December 2018 in Xiangya hospital Central South University, comprising of 21 (65.6%) male and 11 (34.4%) female. The mean age of analytic cohort was 52.94 ± 9.55 years (range 27-67 years). Of all the patients, the mean distance above anal edge was 4.31 ± 2.86 cm (range 0.5-15.0 cm), besides, most of the rectal GIST occurred within 5 cm to the anal edge in 26 (81.2%) of the 32 patients. The longest diameter of rectal GIST was 6.62 ± 4.79 cm (range 0.8-25.0 cm). The most common clinical symptom was change of bowel habits (56.3%), and gene analysis showed most of analytic cohort had kit 11 mutation (59.3%) ( Table 1).  The operative results were summarized in Table 3 Otherwise, the MIS group seemed to gain a shorter time to resume borborygmus after operation, atus passage, resuming oral diet, and hospital stay, but no signi cantly statistic difference(P 0.05). 1 patients in OPEN group had R2 resection while none in MIS group. The length of postoperative hospital stay for patients who had no postoperative complications was longer in the OPEN group comparing with MIS group (6.44 ± 1.33 vs 4.00 ± 1.23 days, P = 0.001). Overall, the rate of postoperative mobility did not signi cantly differed between MIS group and OPEN group in rectal GIST patients(P 0.05). 1 patient got incision infection and another one got anastomotic leakage which nally conducted sigmoidostomy in OPEN group. For the MIS group, 1 patient got postoperative bleeding and cured by local compression for the rst one day after operation, one got anastomotic leakage and conducted sigmoidostomy.

Oncologic Outcomes for rectal GISTs
The median follow-up was 71.55 months for OPEN group and 60.36 months for MIS group. There were no differences in rate of 1-year, 3-year, and 5-year Progression Free Survival and overall survival (Fig. 2-3). No recurrence was observed at the trocar or main surgical wound. During the follow-up period, 6 patients in the OPEN group developed recurrence or metastases (3 liver metastases, 3 local recurrence or pelvic metastases) compared with 5 patients in the MIS group (2 live metastases, 3 local recurrence or pelvic metastases).

Discussion
GIST could occur throughout the gastrointestinal tract, most frequently in the stomach and small intestine, and relatively rare in rectum [9,10]. Our research found that most of rectal GIST occurred in the lower location of the rectum, with 26 (81.2%) of the 32 patients located occurred within 5 cm to the anal edge, besides, Shu P, et al also found that 61(85.9%) of 71 rectal GIST located within 5 cm to the anal edge [11]. Surgical resection is the standard treatment for resectable rectal GIST, and due to the low location in rectum, surgical methods should be carefully considered because it could lead to an extensive organ resection, which might nally change the living habits permanently.
The rst minimally invasive surgery was reported by Philip Mouret of Lyons, France in 1987 [12]. Since then, minimally invsive surgery has widely spread. Compared with tranditional open surgery, minimally invasive procedures are generally supposed as a great development of surgical procedures, which could potentially improve the short-term bene ts, including alleviate surgical pain, a shorter hospital stay and a quicker recovery from operation. Plenty of studies have demonstrated that minimally invasive surgery get a favouratable effeciency in rectal diseases, including rectal cancer and other benign or malignant rectal lesions [13,14]. However, the safety, effeciency, short-term and long-term outcomes of minimally invasive suegry versus open surgery in rectal GISTs still remain to be explore.
The rst concern of MIS in rectal GISTs is the safety. Differing from rectal cancer and the exophytic growing feature of rectal GISTs, their large dimensions, low location of rectum and adherent to the surrounding organs densely. Hence, it might be a challenge for surgeons to have a complete recetion with such narrow pelvic space for open surgery [15]. Therefore, minimally invasive surgery might be an alternative surgical methods, because the latter offers a better structural visualization and easily resect the rectal GISTs with minimal trauma. Yang Z et al reported that transnal surgery has a great bene t in rectal GISTs, including short operation time, less blood loss, quick revovery and low complication rate [16]. Several small scale case reports also indicate that transanal endoscopic and laparoscopic excision is safe and could be an alternative treatment of rectal GISTs [17][18][19]. However, there were no study report the comparision between minimally invasive surgery and open surgery in rectal GISTs. Our research indicated that compared with tranditional open surgery, the minimally invasive surgery was feasible in most of rectal GISTs, none was conversion to open surgery. Additionally, similar postoperative morbidity was found between MIS group and OPEN group. Interestingly, our research found that MIS group recived a shorter operating time and lesser blood less than OPEN group during the operation, indicated that minimally invasive surgery is safety while conducted by experienced surgeons.
The assessment of oncological outcomes is another determining factor for the surgical treatment of rectal GISTs. For other rectal lesions, a systematic review and meta-analysis indicates that laparoscopic surgery for rectal cancer recieves no differences in any oncologic parmeter, disease-free survival and 5- year survival compared with tranditional open surgery [20]. However, Martínez-Pérez A et al found laparoscopic mesorectal excision achieved a higher risk of noncomplete excision compared with open mescorecatal excision, but the long-term outcomes still remained to assess [21]. Differing from rectal cancer, positive resection margins and tumor rupcture are the most important hazard factors for poorer survival in rectal GISTs [6,22]. Hence, surgerons should evaluate and resect tumors carefully without crude procedure. In our center, with careful remove of rectal GISTs both minimally invasive surgery and open surgery by experimental surgeons, none of these patents received R1 section or tumor rupture, otherwise, similar oncologic outcome was obeserved both in MIS group and OPEN group.
Our study have several limitations. First, it is a retrospective study in a experienced center, some confounding variables (such as BMI dietary behavior and others) cannot be compared completely between each group, and due to the low incidence of rectal GISTs, sample size was relative small in this study, which might nally affect the results, further randomized controlled, multiple-center and prospective studies should be performed. Second, we eliminate selection bias and other confounding factors with 5 convariates, there might exist more convariates that could in uence the affect the selection of surgery methods.

Conclusion
Compared with open surgery, minimally invasive surgery bene ts a shorter operating time and lesser blood less during operation in rectal GISTs. Moreover, similar oncologic outcome was found between minimally invasive surgery and open surgery in rectal GISTs.