Impact of Previous Abdominal Surgery on Robotic-assisted Rectal Surgery in Patients With Rectal Cancer Undergoing Preoperative Chemoradiotherapy: A Propensity Score Matching Study

Background: The application of minimally invasive surgery in patients with colorectal cancer (CRC) and a history of previous abdominal surgery (PAS) remains controversial. This retrospective study with propensity score matching (PSM) investigated the impact of PAS on robotic-assisted rectal surgery outcomes in patients with rectal cancer undergoing preoperative concurrent chemoradiotherapy (CCRT). Methods: In total, 203 patients with rectal cancer who underwent preoperative CCRT and robotic-assisted rectal surgery between May 2013 and December 2019 were enrolled. Patients were categorized into PAS and non-PAS groups based on the PAS history. The PSM caliper matching method with 1-to-3 match was used to match PAS patients with non-PAS. Results: Of the 203 enrolled patients, 35 were PAS patients 168 were non-PAS patients. After PSM, 32 PAS patients and 96 non-PAS patients were included for analysis. No signicant between-group differences were noted in the perioperative outcomes, including median console time [165 min (PAS) vs 175 min (noon-PAS), P = 0.4542)] and median operation time [275 min (PAS) vs 290 min (non-PAS), P = 0.5943)] after PSM. Postoperative recovery and overall complication rates were also similar (all P > 0.05). Moreover, the between-group differences in pathological or short-term oncological outcomes were also nonsignicant (all P > 0.05). No 30-day postoperative deaths were observed in either group. Conclusion: The current results indicate that robotic-assisted surgery is safe and feasible for PAS patients with rectal cancer undergoing preoperative CCRT. However, future prospective randomized clinical trials are required to verify these ndings.

5-uorouracil, leucovorin, and oxaliplatin) regimen every 2 weeks and LCRT (totally 5000 cGy in 25 fractions) , as described previously [23]. Patients with cT2 rectal cancer within 5 cm from the anal verge also received the same preoperative CCRT. After radiotherapy, all patients continued the biweekly FOLFOX regimen up to 2-3 weeks before robotic-assisted rectal surgery. Thereafter, abdominal and pelvic CT or high de nition MRI was performed for restaging.
Robotic-assisted TME was performed using the single-docking technique if the rectal cancer was resectable [22]. During surgery, laparoscopic enterolysis was performed rst if peritoneal adhesion was noted. The following clinicopathological features and perioperative parameters were evaluated: age, sex, histological type, TNM (tumor, node, and metastasis) classi cation, vascular invasion, perineural invasion, postoperative serum carcinoembryonic antigen (CEA) levels, tumor location (distance from the anal verge), American Society of Anesthesiologists (ASA) score, and body mass index (BMI) were evaluated.
The TNM classi cation was determined according to the criteria of the American Joint Commission on Cancer (AJCC) and International Union Against Cancer (UICC) [24]. The tumor regression grade (TRG) was evaluated according to the AJCC and College of American Pathologists regression grade [25]. Perioperative outcomes, including surgical procedures, docking time, console time, operation time, estimated blood loss, duration of the rst atus passage, duration for resuming a soft diet, duration of postoperative hospital stay, and postoperative rst day visual analog scale (VAS) pain score were evaluated.
After robotic-assisted surgery, adjuvant chemotherapy was administrated, as reported previously [24]. In brief, an additional 5-6 cycles of the FOLFOX regimen were administered every 2 weeks (12 perioperative cycles in total) for patients with the following risk factors: (1) ypN+, (2) positive circumferential resection margin (CRM) or distal resection margin (DRM), and (3) ypT3-4. For patients with ypT1-2N0 lesions, uoropyrimidine-based chemotherapy was administrated for up to 6 months of perioperative chemotherapy. Patients were followed up regularly, with their clinical outcomes and survival statuses being recorded, as described previously [24].

Statistical Analysis
To reduce the potential selection bias, we used PSM to match the compatible groups. The PSM caliper matching method with 1-to-3 match was used to match PAS patients with non-PAS patients without. The covariates included patient demographic characteristics (age and sex), clinical cancer stage (including Tand N-staging), tumor location (distance from the anal verge), ASA score, and BMI. All data were fully anonymized before they were accessed. All data were statistically analyzed using the Statistical Analysis System (SAS) software, version 9.4 (SAS Institute Inc., SAS Campus Drive, Cary, North Carolina 27513, USA). All patients were followed up until their death or last follow-up, whichever occurred rst. The docking time was de ned as the time required to position the robot and secure the robot arms to the corresponding port sites. The console time was de ned as the total duration of any robotic-assisted surgical procedure using the robotic system. The operation time was de ned as the time between the initial skin incision and wound closure completion. A P value of < 0.05 indicated statistical signi cance. Disease-free survival (DFS) was de ned as the time from the date of primary treatment to the date of diagnosis of recurrent or metastatic disease or the date of last follow-up, whereas overall survival (OS) was de ned as the time from the date of primary treatment to the date of death from any cause or last follow-up. DFS and OS were determined using the Kaplan-Meier method, and the log-rank test was performed to compare time-to-event distributions.

Patient Characteristics and Perioperative Outcomes
Between May 2013 and December 2019, 369 patients with rectal cancer underwent robotic-assisted surgery. OF the patients, 203 patients who met the including criteria were enrolled in this study. Of them, 35 had a history of PAS, whereas 168 did not. After PSM, 32 PAS and 96 non-PAS patients were included for analysis (Fig. 1). The baseline characteristics and perioperative outcomes of the patients before (n = 203) and after (n = 128) PSM are summarized in Table 1.
Anastomosis stenosis was observed in 3 (9.4%) PAS and 2 (2.1%) non-PAS patients after PSM. Based on the Clavien-Dindo classi cation system, all postoperative ileus, urinary complication, central venous catheter infection, neck cellulitis, sexual dysfunction, and pulmonary complications were of grade I and the patients demonstrated an uneventful recovery course after conservative treatment. Moreover, no 30-day hospital mortality occurred.

Discussion
In the present study, we compared the perioperative outcomes, postoperative pathological outcomes, and oncological outcomes of preoperative CCRT and robotic-assisted rectal surgery between PAS and non-PAS patients with CRC. To minimize selection bias, we performed PSM between the patient groups and found no signi cant between-group differences in perioperative outcomes, postoperative pathological outcomes, and oncological outcomes both before and after PSM.
Before PSM, the PAS group included signi cantly more women than men (62.9% vs. 37.1%, P = 0.006), consistent with a previous study [18]. This signi cant difference was due to common gynecologic surgical procedures, including abdominal total hysterectomy, cesarean section, and cesarean section, being commonly employed in female patients. Here, 20 (90.9%) of 22 female PAS patients underwent the aforementioned procedures, which may have caused adhesions in the pelvic cavity and increased the di culty of robotic-assisted rectal surgery and the risk of perioperative complications. Although the median console time was signi cant shorter in PAS patients than in non-PAS patients before PSM, the median operation time was not signi cantly different between the two groups before or after PAM. These ndings are consistent with those reported previously [18]. Studies evaluating the impact of PAS on laparoscopic colorectal surgical outcomes [14][15][16][17][18] have found no signi cant between-group differences in the operation time. However, in a large case-control study on 756 patients [19], Zeng et al. found that PAS was associated with longer operation time (220 vs. 200 min, P = 0.002). In the present study, other perioperative outcomes were similar between the groups, consistent with previous results [18].
Similarly, in the current study, the overall complication rates and speci cally anastomosis leakage and postoperative ileus rates did not differ signi cantly between the groups before or after PSM corroborating the previous results [18].
We also evaluated the impact of PAS on postoperative pathological and oncological outcomes and found nonsigni cant between-group differences before and after PSM. Intraabdominal adhesion may increase surgical di culty, and most intraabdominal adhesions may result from abdominal surgical procedures. Therefore, PAS could also result in surgical di culties. Kang et al. [26] reported that technical di culties during laparoscopic surgery for CRC could negatively affect oncologic safety. By contrast, Lee et al. [17] demonstrated that technical di culties due to intraperitoneal adhesions do not impede the oncologic safety of patients with CRC undergoing laparoscopic surgery. These ndings are consistent with those of Zeng et al. [19], who found nonsigni cant differences in the 3-year DFS and 3-year OS in their case-control study.
To the best of our knowledge, few studies have evaluated the impact of PAS on robotic-assisted colorectal surgical outcomes [18,21]. Park et al. [18] investigated the impact of PAS on robotic-assisted colorectal surgery in 238 patients with CRC (87 patients with colon cancer and 151 patients with rectal cancer). In the present study, we evaluated the impact of PAS on robotic-assisted rectal surgery in 203 patients with rectal cancer, all of whom underwent preoperative CCRT. By contrast, in the aforementioned study [18], only 29 (12.2%) patients underwent preoperative CCRT. Moreover, in the present study, 140 (68.9%) patients had stage III disease, whereas only 89 (37.4%) patients had stage III disease in the aforementioned study [18]. However, our perioperative outcomes, namely operation time, estimated blood loss, and time of resuming soft diet, were comparable with those of the aforementioned study [18]. Hu et al. [21] conducted a meta-analysis to evaluate the effect of PAS on perioperative recovery outcomes of robotic-assisted colorectal surgery; the authors determined an objective conclusion by comparing perioperative outcomes and provided level I evidence for clinical decision making [21].
The current study has several limitations. First, this was a single-center retrospective study with a small sample size (n = 203 patients, including 35 PAS and 168 non-PAS patients). However, we further used PSM to match the compatible groups and reduce the potential selection bias. Second, the retrospective nature of this study, prevented evaluation of the actual severity of intraabdominal adhesions, which may affect the di culties of robotic-assisted rectal surgical procedures. Third, the follow-up interval was relatively shorter, with a median follow-up of 28 months; thus, only the 1-and 3-year oncological outcomes were documented. Fourth, we did not evaluate the postoperative outcomes of urinary, sexual functions, or anal functions.

Conclusion
In the present study, PAS and non-PAS patients demonstrated similar perioperative outcomes and short-term oncological outcomes of robotic-assisted rectal surgery, without any effect on the overall complication rate. Therefore, robotic-assisted surgery may be safe and feasible in PAS patients with rectal cancer undergoing preoperative CCRT. However, further research including a longer follow-up duration investigating the long-term oncological outcomes are warranted. Moreover, prospective randomized clinical trials are required for validating the present results.

Consent for publication
Not applicable.

Availability of data and material
All data used to support these ndings are included in the article.

Competing interests
The authors declare that they have no competing interests.

Funding
This study did not receive any type of funding.