This multicenter, retrospective study investigated the relationship between IBS and long-term outcomes of patients who underwent BTS for obstructive CRC with SEMS insertion. In the survival curves of patients with each pre-stent and post-stent IBS, pre-LMR was associated with significant differences in RFS (p = 0.015) and post-LMR was associated with significant differences in OS (p = 0.030). Uni- and multivariate analyses revealed pre-LMR as a predictor for RFS.
Patients with obstructive CRC often present with poor general condition, and performing emergency surgery without adequate preoperative evaluation and bowel decompression not only leads to an increased rate of stoma formation, resulting in a decrease in quality of life (QOL), but also contributes to elevated morbidity and mortality rates [18]. SEMS provide effective bowel decompression, facilitating oral intake and thus improving nutritional status and enhancing QOL. In addition, SEMS offer the advantage of allowing preoperative endoscopic searches for synchronous cancers or other lesions upstream of the stenotic site, as well as enabling evaluation of the condition of the colon through endoscopic examination, which can serve as a reference for determining the extent of resection and the optimal surgical approach. In fact, the frequency of synchronous multiple cancers in obstructive CRC is reported to be around 8% [19]. In this study, which specifically focused on patients who underwent BTS for obstructive CRC with SEMS insertion, we identified synchronous CRC in 6 of 278 cases (2.2%). Furthermore, among the 3435 cases that underwent surgery for CRC, SEMS insertion was performed in 278 cases (8.1%), and the number of cases with SEMS insertion is anticipated to continue increasing in response to the rising incidence of CRC.
Cancer-associated systemic inflammatory response has garnered attention as a significant indicator of tumor progression, and numerous prior studies have reported on useful IBS for predicting prognosis. These scores can be calculated using routine blood test results, making them convenient. In previous studies, various IBS such as LMR, NLR, PLR, PNI, CAR, SII, GPS, mGPS, GRIm-score, and others have been reported. Abnormalities in white blood cell differentials such as an increase in neutrophil and monocyte counts or a decrease in lymphocyte count often occur in cancer patients. Neutrophils can promote tumor cell proliferation, angiogenesis, and distant metastasis, while lymphocytes play mainly a role in anti-tumor defense. Lymphocytes induce cytotoxic cell death and produce cytokines that inhibit the proliferation and metastatic activity of cancer cells [20]. Furthermore, changes in lymphocyte counts can reportedly impact the prognosis of CRC patients [21–23]. Monocytes also play a crucial role in tumor progression within the tumor microenvironment [24]. Pro-inflammatory cytokines such as tumor necrosis factor alpha and interleukin 1 secreted by monocytes are associated with poor prognosis in cancer patients [25]. In the course of neoplastic disease, monocytes differentiate into tumor-associated macrophages (TAMs) and may promote tumor cell death [26]. On the other hand, they exhibit pro-cancerous properties, such as suppression of acquired immunity, facilitating angiogenesis, invasion, and migration, all of which can facilitate tumor invasion and metastasis [27]. An increase in monocyte count may reflect the activity of TAMs. A low LMR therefore indicates a decrease in lymphocyte count and/or an increase in monocyte count, which is associated with poor prognosis.
Only two reports have identified an association between obstructive CRC and IBS. Chen et al. reported that preoperative derived NLR and LMR, respectively, could predict OS and DFS in patients undergoing emergency surgery and BTS between 2008 and 2015, and BTS via SEMS insertion might be preferable for obstructive CRC patients with low preoperative LMR [16]. Sato et al examined the relationship between preoperative IBS (PNI, NLR, LMR, and PLR) and long-term survival in obstructive CRC patients with pathological stage 2 or 3 who underwent BTS with SEMS insertion between 2009 and 2018. Their results showed that the PNI was a potent prognostic indicator [17]. We note that the present study is the first to report the association between pre-stent IBS and the prognosis of patients who underwent BTS for obstructive CRC with SEMS insertion. Furthermore, the cutoff value for LMR has been around approximately 3 in previous reports, and the pre-LMR of 3.3 in this study was deemed appropriate [28, 29].
In this study, each score was measured at two points (pre- and post-stent insertion), and examined the impact on long-term outcomes. For obstructive CRC patients undergoing BTS with SEMS insertion, the timing of measuring inflammation-related serum parameters is believed to significantly affect the results. Previous reports have often focused on post-stent IBS. However, since preoperative test values can be influenced by the success rate and duration of SEMS insertion, cases may exist where these scores may not correlate with prognosis. Specifically, before SEMS insertion, factors such as the extent of tumor progression itself and the impact of obstructive colitis may be in play. After SEMS insertion, influences could arise from the resolution of obstructive colitis due to the relief of luminal obstruction, inflammation resulting from stent expansion at the stenotic site, and the impact of tumor progression during the waiting period until surgery, among other factors. The present study focused on pre-LMR based on blood tests when patients consulted for obstructive symptoms, we reported pre-LMR as a prognostic factor for Stage 2 and 3 obstructive colorectal cancer patients with SEMS insertion who underwent BTS for obstructive CRC. We investigated the relationship between changes from pre- to post-stent IBS and prognosis, but none of these showed any correlations. One factor was the limited number of cases in the present study because of the presence of cases with incomplete data. Both systemic inflammation and nutritional status, along with their changes, appear important for estimating the prognosis of obstructive CRC patients. Further research is needed to elucidate the mechanisms involved.
The present study showed several limitations. First, this was a retrospective study and the cohort comprised patients who underwent BTS for obstructive CRC with SEMS insertion. Second, we analyzed only pathological stage 2 or 3 patients who underwent BTS for obstructive CRC, and excluded patients with pathological stage 1 or 4 disease, or who received neoadjuvant chemotherapy. Third, a wide range of durations of preoperative SEMS insertion was seen for subjects in this study. Further positive evaluation is desired to resolve this issue, and large-scale studies or randomized controlled trials are needed.
In conclusion, LMR is a readily measurable biomarker and pre-LMR-L serves as a prognostic factor for postoperative recurrence in patients who undergo BTS for obstructive CRC with stent insertion. There is potential for LMR to serve as an indicator for aggressive treatments such as adjuvant chemotherapy for obstructive CRC patients.