In this study, the group with time interval of 11–17 days from stenting to elective surgery was found to show favorable short-term outcomes than the group with time interval < 11 days or > 17 days. Benefits of a time interval of 11–17 days included shorter hospital days than the time interval < 11 days and a lower proportion of stoma formation than the time interval > 17 days. In addition, there was no significant difference in OS or DFS between time interval groups (< 11 days, 11–17 days, > 17days) and the ES group. In the multivariable analysis for OS, only the group with time interval of 11–17 days showed a favorable outcome compared to the ES group. Time interval of 11–17 days was verified to have advantages in surgical outcomes compared to time interval < 11 days or > 17 days. There was no significant difference in long-term outcomes between ES and time interval groups. Hence, a time interval of 11–17 days was presumed to be optimal.
The strength of this study was that it was the first study to compare oncologic safety between time interval groups of SEMS and the ES group. Despite there is a clinical interest in appropriate time intervals from stenting to surgery, previous studies have not compared SEMS groups categorized by time interval to the ES group. In addition, we included a more significant number of patients than previous studies.
Our results support that the optimal time interval is around two weeks, consistent with the updated ESGE guideline1 and a recent multicenter study.15 In that multicenter study, time interval > 17 days showed a lower proportion of laparoscopic resection compared to time interval of 5–10 days. Contrarily, postoperative complications were more frequent in the group with time interval of 5–10 days than in the group with time interval > 17 days, whereas there was no significant difference in surgical outcomes between time intervals of 5–10 days and 11–17 days or between time intervals 11–17 days and > 17 days.15 In previous studies, time interval ≥ 10 days was associated with primary anastomosis19 and time interval ≤ 15 days had a lower risk of postoperative complication than others,20 whereas the risk of recurrence increased in the time interval ≥ 18 days.21 Furthermore, in a recent study, the DFS was significantly worse in time interval ≥ 16 days than in time interval < 16 days, with time interval ≥ 16 days being reported as an independent risk factor for recurrence.22 Contrarily, a recent study has suggested that time interval < 8 days has favorable long-term outcomes such as DFS and OS than time interval of 8–14 days or > 14 days;16 however, the reason for those findings was lacking with limitations owing to the retrospective nature of this study. Based on accumulated reports, about two weeks as an interval to surgery is acceptable. Our results also support this finding.
It is unclear why an appropriate time interval is important and which factors are involved in such finding. Presumably, a short break between stenting and elective surgery might be associated with insufficient restoration from ischemic injury or bowel edema. An ischemic injury could occur incidentally, ranging from 1–7% in patients with malignant bowel obstruction due to upstream bowel distension or abnormal stagnant of intestinal bacteria.23–25 In addition, bowel edema changing within 1–2 weeks after stenting was related to difficult manipulation during surgery.26 Considering this, it is necessary to have an appropriate interval when ischemic colitis associated with malignant obstruction is expected to improve and intestinal edema after stenting is anticipated to subside. It is also ambiguous why a long time interval is associated with poor prognosis. Recent studies have shown consistent results that a longer time interval is associated with poor prognosis. Especially, a time interval ≥ 35 days increased the risk of recurrence significantly (HR: 16.6, 95% CI: 2.21–125).16,22 Regarding potential factors, the pressure effect by SEMS placement might induce the dissemination of tumor cells, which was raised due to findings showing increased perineural invasion in specimens after surgery.27,28 However, whether perineural invasion has a negative effect on long-term outcomes has inconsistent results.28–30 We also found that the proportion of perineural invasion in the SEMS group was higher than that in the ES group, whereas perineural invasion was not related to OS or recurrence. Another concern is that stent insertion might increase levels of viable circulating tumor cells,31 circulating CK20 mRNA,32 cell-free DNA, and circulating tumor DNA33 in peripheral blood in molecular studies. Thus, an issue about oncologic safety is raised. However, patients enrolled in the SEMS group were fewer than thirty in those studies and some patients were in a palliative stage. Furthermore, those studies could not verify adverse effects on long-term outcomes. To date, having a long time interval from SEMS placement to elective surgery is related to an unfavorable prognosis.
Compared to ES, SEMS can give time to prepare for surgery in consideration of the patient's underlying disease.34 It enables the evaluation of synchronous premalignant or malignant lesions.35 In addition, bowel preparation before surgery can reduce the risk of surgical site infection and anastomosis leakage.36–38 Moreover, SEMS placement exerts a low rate of stoma formation after surgery.3,4,10 We also found that the SEMS group had favorable surgical outcomes with a higher proportion of laparoscopic approach, lower amount of EBL, and shorter hospital days than the ES group. The incidence of major adverse events after surgery was also lower in the SEMS group than in the ES group, although such difference was not statistically significant. However, it is necessary to pay attention to complications. Stent has a perforation risk of about 8%.9,39 Perforation can increase the risk of local recurrence.40,41 Some meta-analyses have shown an increased risk of recurrence in the SEMS group than in the ES group.2,3,42 In contrast, other meta-analyses have found no significant difference in DFS or OS.2,7,9,10,12,20 Overall, it is judged that various advantages of SEMS placement as a bridge to surgery outweigh potential risks if it satisfies indications for stent insertion. Additionally, there is a necessity to consider an adequate time interval.
This study had several limitations. There might be selection bias owing to its retrospective nature. All patients in the ES group were initially admitted to the emergency room and subsequently treated by ES. Some patients in the SEMS group initially visited outpatients clinic, not the emergency room. However, patients in the SEMS group were selected based on the exact inclusion and exclusion criteria. We found that the group with time interval of 11–17 days showed improved OS compared to the ES group in the multivariable analyses. Further studies are necessary to determine whether this finding is real and what are weighted factors. We included rectal cancer as well despite a low proportion. The approach of treatment between colon cancer and rectal cancer is slightly different, such as neoadjuvant therapy. Thus, there might be a possibility of heterogeneity.43,44
In this study, the group with time interval of 11–17 days showed favored surgical outcomes compared to the group with time interval < 11 days or > 17 days. There was no significant difference in long-term effects between time intervals after stenting and ES. Therefore, time interval of around two weeks is reasonable based on the accumulated evidence.