The Short and Long Oncological Outcome of Indocyanine Green for Lateral Lymph Node Dissection in Mid-low Rectum Cancer

The Short and Long Oncological Outcome of Indocyanine Green for Lateral Lymph Node Dissection in Mid-low Rectum Cancer | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article The Short and Long Oncological Outcome of Indocyanine Green for Lateral Lymph Node Dissection in Mid-low Rectum Cancer Wenlong Qiu, Yu Liu, Shiwen Mei, Jichuan Quan, Yuegang Li, Qian Liu This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-5570995/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 9 You are reading this latest preprint version Abstract Background Lateral lymph node dissection (LLND) is a key component of surgical treatment for locally advanced mid-to-lower rectal cancer. While indocyanine green (ICG) fluorescence guidance has been proposed to enhance surgical precision, its impact on long-term oncological outcomes remains unclear. Methods This retrospective, multicenter study compared ICG-assisted laparoscopic LLND (ICG-LND) with conventional laparoscopic LLND in patients with mid-to-lower rectal cancer between January 2018 and June 2022. Outcomes included 3-year overall survival (OS), recurrence-free survival (RFS), local recurrence rates, and distant metastasis rates. Kaplan-Meier analysis and Cox proportional hazards regression models were used to evaluate survival outcomes. Results The study included 258 patients (ICG-LND: 79; control: 179). The ICG-LND group had a slightly higher median number of harvested lateral lymph nodes (9 [IQR: 5–13] vs. 7 [IQR: 4–13]), but the difference was not significant (P = 0.611). Similarly, positive lateral lymph node counts showed no significant difference (P = 0.455). Median postoperative hospital stays were shorter in the ICG-LND group (6 [IQR: 5–8] vs. 7 [IQR: 6–9] days, P < 0.001). Survival analysis showed no significant differences between groups in OS (5-year: 84.6% vs. 86.1%, P = 0.884), RFS, or recurrence rates (local: 6.3% vs. 6.7%; distant: 10.1% vs. 10.8%). Conclusion ICG-LND shortens postoperative recovery but does not enhance long-term oncological outcomes, including survival and recurrence rates. Further prospective studies are needed to validate its prognostic value. Indocyanine green Lateral lymph node dissection Rectal cancer Fluorescence-guided surgery Oncological outcomes Figures Figure 1 Figure 2 Figure 3 Introduction Lateral lymph node dissection (LLND) is a crucial component of the surgical treatment for local advanced colorectal cancer, particularly in patients at high risk of lateral lymph node metastasis. Accurate identification and thorough dissection of these nodes are vital to achieving optimal oncological outcomes. Failure to address lateral lymph node metastasis appropriately can lead to increased local recurrence rates and compromised survival [ 1 – 3 ] . The introduction of indocyanine green (ICG), a near-infrared fluorescent dye, has been hailed as a significant advancement in enhancing the accuracy and effectiveness of LLND. By enabling real-time, intraoperative visualization of lymphatic structures and blood flow, ICG may facilitate more comprehensive lymph node clearance and reduce postoperative complications, such as anastomotic leakage [ 4 – 6 ] . The utility of ICG in colorectal cancer surgery extends beyond LLND. It has been used in evaluating bowel perfusion during anastomosis, identifying sentinel lymph nodes, and mapping lymphatic drainage, all of which are crucial for improving surgical outcomes [ 7 – 9 ] . The use of ICG in LLND specifically has shown promise in improving the detection and excision of metastatic lymph nodes that might otherwise be missed by conventional methods. By enhancing the precision of nodal dissection, ICG is hypothesized to contribute to better long-term outcomes, such as reducing local recurrence rates and improving overall survival. However, the actual impact of ICG-guided LLND on colorectal cancer prognosis remains a topic of ongoing international debate. Globally, a growing body of evidence supports the use of ICG in colorectal cancer surgery. A study from Japan suggests that ICG may enhance the quality of laparoscopic LPLND and improve local control of the lateral pelvis, leading to better postoperative outcomes [ 10 , 11 ] . However, this study did not elaborate on the impact of ICG on the short-term oncological outcomes of rectal cancer patients undergoing LLND, such as the number of retrieved lymph nodes, intraoperative blood loss, postoperative complications, and hospital stay. Additionally, the sample size was relatively small (n = 172). In China, the adoption of ICG in colorectal cancer surgery has been met with cautious optimism. Chinese studies have reported that ICG-guided LLND improves lymph node clearance, however, In China, studies have demonstrated the safety and feasibility of ICG in LLND for rectal cancer, particularly in terms of short-term outcomes [ 12 – 14 ] . However, there is still a lack of sufficient research on its long-term oncological prognosis. Therefore, our study aims to critically evaluate the role of ICG in LLND, focusing on whether this technique leads to improved oncological outcomes, such as lower recurrence rates and enhanced overall survival, compared to traditional methods. Through a comprehensive analysis of both domestic and international data, we seek to clarify the prognostic value of ICG and contribute to the ongoing debate regarding its efficacy. Materials and methods Patient Population This retrospective, multi-center study aimed to evaluate the effectiveness of ICG-assisted laparoscopic LLND (ICG-LND) compared to conventional laparoscopic LLND without ICG, using propensity score matching for comparison. The study involved patients who underwent laparoscopic LLND for mid and lower rectal cancer between January 2018 and June 2022 (Fig. 1 ). The study period concluded on 30 September 2024, and patients lost to follow-up before this date were censored at their last documented visit, and the median follow-up time was 48.2 months. The research protocol received approval from the Ethics Advisory Committee of the Chinese Academy of Medical Sciences Cancer Hospital, as well as from the institutional review boards of each participating center. Given the retrospective design of the study, written informed consent was not required, and an opt-out method was employed to disclose study details. The study was registered with the Chinese Clinical Trial Registry. Eligibility Criteria Inclusion criteria for this study were: (1) rectal cancer patients aged 18 or older; (2) histologically confirmed cases of adenocarcinoma; (3) clinical stage I–III; (4) tumor location within 100 mm from the anal verge (AV); and (5) patients who underwent laparoscopic LLND. Patients were excluded if they: (1) younger than 18 or older than 80 years, (2) were preoperatively diagnosed with distant metastasis at first diagnosis, (3) had undergone total pelvic exenteration, or (4) combined resection with other organs. Fluorescence-Guided Lymph Node Dissection Three research centers with a long-term collaboration formed a lateral lymph node management consortium. The similar ICG-LND protocols and implemented standardized training was adopted on ICG administration, ensuring procedural consistency and minimizing bias. In the ICG-LND group, indocyanine green (ICG) was administered via submucosal injection. A dose of 0.25 mg/kg of ICG was injected into the submucosal layer around the tumor approximately one hours before surgery to allow for optimal uptake by the local lymphatic system. During surgery, near-infrared (NIR) fluorescence imaging was used to map the lymphatic pathways and highlight lateral lymph nodes. The fluorescent signal enabled surgeons to more accurately identify and dissect lymph nodes, potentially improving the precision and completeness of lymph node clearance (Fig. 2 ). During the procedure, a laparoscopic NIR camera system was used to visualize the fluorescent signal from the lymph nodes and surrounding lymphatic vessels. Surgical Technique for Lateral Lymph Node Dissection Lateral lymph node dissection (LLND) was performed following a standardized laparoscopic technique by experienced surgeons certified in laparoscopic total mesorectal excision (TME). A 5-port approach was typically employed, with 12 mm trocars placed at the umbilicus and right lower abdomen, and 5 mm trocars placed in the right upper, left upper, and left lower abdomen. Key areas targeted for dissection included the internal pudendal artery and the obturator artery, as these are common sites for pelvic lymph node metastasis and require careful preservation of autonomic nerves. The dissection began with the ureteric hypogastric fascia, preserving the ureter and hypogastric nerve as a unified membranous structure. The lymph nodes in the obturator region were then accessed by dissecting the lateral pelvic wall, involving the psoas major and internal obturator muscles. After dividing the medial umbilical ligament, the bladder hypogastric fascia was dissected to remove lymph nodes in the obturator region. Throughout this process, care was taken to preserve the obturator nerve, while the obturator vessels were transected. Dissection continued around the internal iliac and pudendal arteries, extending to the Alcock canal. The internal pudendal artery, along with its subvesical branches, was selectively ligated, and the inferior vesical artery and vein were severed distal to their junction with the bladder, ensuring complete autonomic nerve preservation. Fluorescence-Assisted Lymphatic Mapping The ICG-stained lymph nodes, including the internal iliac (No. 263), obturator (No. 283), external iliac (No. 293), and common iliac lymph nodes (No. 273), were identified using the NIR camera system. The fluorescent lymphatic drainage patterns, lymph nodes, and connecting lymphatic vessels were compared to the branching patterns of the iliac vessels to delineate the boundaries for lymph node dissection. The procedure for LLND in patients who received NIR guidance was essentially the same as in those who did not. Postoperative Follow-Up After discharge, patients were monitored with tumor markers (CEA, CA 19–9) and CT scans every 3 months for the first 2 years and every 6 months for 3 to 5 years to assess for any recurrence or metastasis. Statistical Analysis The primary outcomes was overall survival (OS), and the 3-year recurrence free survival (RFS), local recurrence (LR) rate, and distant metastatic (DM) rate were also analyzed. Data were presented as median values with interquartile ranges (IQR). Categorical and continuous variables were compared using Pearson’s chi-square test and the Mann–Whitney U test, respectively. Survival outcomes (OS, RFS, LR, LLR) were evaluated using the Kaplan–Meier method and the log-rank test. A p-value of less than 0.05 was considered statistically significant, and all analyses were conducted using IBM SPSS Statistics version 23.0 (IBM Corp., Somers, NY, USA). Results Patient Characteristics and Tumor Profiles Among the 258 patients included, the ICG-LND group had a significantly younger mean age compared to the control group (56.0 ± 10.8 vs. 58.9 ± 11.1 years, P = 0.048), while other baseline characteristics, including sex distribution and BMI, showed no significant differences. Clinical tumor (cT) and nodal (cN) statuses were comparable between groups, with advanced cT3–4 and cN1–2 predominating in both. Pathologically, the ICG-LND group had a higher proportion of early-stage tumors (pT1–2: 51.9% vs. 36.9%, P = 0.024) but no differences in nodal status or overall pathologic stage. Poorly differentiated tumors were more frequent in the ICG-LND group (48.1% vs. 32.4%, P = 0.016), while lymphatic, vascular, and perineural invasion rates, as well as tumor size and neoadjuvant chemotherapy use, were similar across groups. Surgical Outcomes and Postoperative Recovery In the comparison of surgical outcomes between the control group and the ICG-LND group, the median number of harvested lateral lymph nodes was slightly higher in the ICG-LND group (9 [IQR: 5–13]) compared to the control group (7 [IQR: 4–13]), but the difference was not statistically significant (P = 0.611). Similarly, the number of positive lateral lymph nodes did not differ significantly between groups (P = 0.455). However, the ICG-LND group demonstrated a significantly higher total number of harvested lymph nodes (28 [IQR: 23–37] vs. 26 [IQR: 19–37], P = 0.042), suggesting improved overall lymph node retrieval. Despite this, the number of positive total nodes remained similar between the two groups (P = 0.962). Notably, the postoperative hospital stay was significantly shorter in the ICG-LND group (6 [IQR: 5–8] days vs. 7 [IQR: 6–9] days, P < 0.001), indicating potential benefits in postoperative recovery. No significant differences were observed between the control group and the ICG-LND group in terms of estimated blood loss (50 mL [20, 60] vs. 30 mL [20, 100], P = 0.765), operating time (240 minutes [200, 305] vs. 251 minutes [200, 290], P = 0.523), or complication rates (P = 0.871). Specifically, the complication rates included intraoperative bleeding (4 vs. 2), anastomotic leakage (7 vs. 3), ileus (3 vs. 1), and incisional infection (3 vs. 1) for the control and ICG-LND groups, respectively. These findings suggest that while ICG-LND does not significantly increase lateral lymph node retrieval, it may contribute to enhanced overall lymph node dissection and improved postoperative recovery. Patterns of Clinical Failure In the cohort, there were no significant differences in patterns of distant metastasis between the control and ICG-LND groups. Lung metastases were observed in 17 patients (9.5%) in the control group and 7 patients (8.9%) in the ICG-LND group ( P = 0.871), while liver metastases occurred in 9 (5.0%) and 4 (5.1%) patients, respectively ( P = 0.767). Local recurrence patterns were also comparable between the groups. Anastomotic recurrence occurred in 4 patients (2.2%) in the control group and 1 patient (1.3%) in the ICG-LND group ( P = 0.976). Central pelvic recurrence was slightly higher in the control group (17 [9.5%] vs. 4 [5.1%], P = 0.230), and lateral pelvic recurrence was noted in 7 (3.9%) and 2 (2.5%) patients, respectively ( P = 0.851). No significant differences in clinical failure patterns were observed between the two groups across all evaluated parameters. Kaplan-Meier Survival Analysis and Recurrence Rates The Kaplan-Meier survival analyses (Fig. 3 ) revealed no significant differences between the ICG-LND group (n = 79) and the control group (n = 179) over a 60-month follow-up period for overall survival (P = 0.884), recurrence-free survival (P = 0.789), or local recurrence rates (P = 0.822). At the 3-year mark, the overall survival rates were 92.4% for the ICG-LND group and 93.2% for the control group, while the recurrence-free survival rates were 88.1% and 89.6%, respectively. Both groups demonstrated closely aligned survival curves and comparable local recurrence rates, suggesting that the application of ICG in lymph node dissection does not adversely affect these outcomes. Furthermore, the longitudinal data analysis, including the 3-year recurrence rates, showed no significant differences in either local or distant metastatic recurrence between the two groups, with the cumulative recurrence rates remaining low (local recurrence: 6.3% in the ICG-LND group vs. 6.7% in the control group; distant metastasis: 10.1% vs. 10.8%). These consistent findings across multiple survival and recurrence endpoints indicate that ICG-guided lymph node dissection does not improve local control rates or survival outcomes, highlighting its lack of impact on long-term oncological prognosis. The results of the Cox regression analyses In the univariate analysis for OS (Table 4 ), factors such as age (≥ 60 years), pN stage (N + vs. N0), and lymphatic invasion (Yes vs. No) were found to be significant. However, when adjusting for potential confounders in the multivariate analysis, only age (HR = 1.762, 95% CI: 1.361–2.610, P = 0.047) and pN stage (HR = 1.574, 95% CI: 1.097–2.771, P = 0.014) remained significant. Interestingly, ICG-guided lymph node dissection (ICG-LND) did not show a significant effect on OS (HR = 0.936, 95% CI: 0.425–2.063, P = 0.870). Table 1 Patient characteristics. Variable Total (n, %) Control (n, %) ICG-LND (n, %) P (n = 179) (n = 79) Age, yr (Mean ± SD) 56.0 ± 10.8 58.9 ± 11.1 0.048 < 60 143 (55.4) 103 (57.5) 40 (50.6) 0.303 ≥ 60 115 (44.6) 76 (42.5) 39 (49.4) Sex 0.461 Female 112 (43.4) 75 (41.9) 37 (46.8) Male 146 (56.6) 104 (58.7) 42 (53.2) BMI (kg/m2, Mean ± SD) 24.6 ± 3.1 23.8 ± 3.6 0.090 < 24 109 (42.2) 73 (40.8) 36 (45.6) 0.473 ≥ 24 149 (57.8) 106 (59.2) 43 (54.4) cT status 0.168 cT 1–2 65 (25.2) 35 (19.6) 30 (.38.0) cT 3–4 193 (74.8) 144 (80.4) 49 (62.0) cN status 0.558 cN 0 88 (34.1) 59 (33.0) 29 (36.7) cN 1–2 170 (65.9) 120 (67.0) 50 (63.3) pT status 0.024 pT 1–2 107 (41.5) 66 (36.9) 41 (51.9) pT 3–4 151 (58.5) 113 (63.1) 38 (48.1) pN status 0.385 pN 0 104 (40.3) 69 (38.5) 35 (44.3) pN 1–2 154 (59.7) 110 (61.5) 44 (55.7) Neoadjuvant chmotherapy 0.376 Yes 125 (48.4) 90 (50.3) 35 (44.3) No 133 (51.6) 89 (49.7) 44 (55.7) Pathologic stage 0.473 I-II 109 (42.2) 73 (40.8) 36 (45.6) III 149 (57.8) 106 (59.2) 43 (54.4) Tumor size (cm, Mean ± SD) 4.0 ± 1.7 4.1 ± 1.6 0.624 ≤ 4.0 157 (60.9) 111 (62.0) 46 (58.2) 0.566 > 4.0 101 (39.1) 68 (38.0) 33 (41.8) Differentiation 0.016 Well/Moderate 162 (62.8) 121 (67.6) 41 (51.9) Poorly 96 (37.2) 58 (32.4) 38 (48.1) Lymphatic invasion 0.384 Negative 170 (65.9) 121 (67.6) 49 (62.0) Positive 88 (34.1) 58 (32.4) 30 (38.0) Vascular invasion 0.222 Negative 177 (68.6) 127 (70.9) 50 (63.3) Positive 81 (31.4) 52 (29.1) 29 (36.7) Perineural invasion 0.182 Negative 153 (59.3) 111 (62.0) 42 (53.2) Positive 105 (40.7) 68 (38.0) 37 (46.8) Table 2 The surgical outcom of control group and ICG-LND group (n = 258). Variants Control (n = 179) ICG-LND (n = 79) P Number of harvested lateral lymph nodes, median (IQR) 7 (4,13) 9 (5,13) 0.611 Number of positive lateral lymph nodes, median (IQR) 0 (0,0) 0 (0,1) 0.455 Number of harvested total nodes, median (IQR) 26 (19,37) 28 (23,37) 0.042 Number of positive harvested total nodes, median (IQR) 1 (0,4) 1 (0,3) 0.962 Postoperative hospital stay (day), median (IQR) 7 (6,9) 6 (5,8) < 0.001 Estimated blood loss (ml), median (IQR) 50 (20,60) 30 (20,100) 0.765 Operating time (min), median (IQR) 240 (200,305) 251 (200,290) 0.523 Complications 0.871 intraoperative bleeding 4 2 anastomotic leakage 7 3 ileus 3 1 incisional infection 3 1 Table 3 Patterns of clinical failure. Variants Control (n = 179) ICG-LND (n = 79) P Distant metastasis Lung 17 7 0.871 Liver 9 4 0.767 Local recurrence Anastomotic 4 1 0.976 Central pelvis 17 4 0.230 Lateral pelvis 7 2 0.851 Table 4 The Cox regression of OS for patients Clinicopathological variables OS Univariate analysis Multivariate analysis HR 95% CI P HR 95% CI P Age (≥ 60 vs. <60) 1.168 1.078–2.101 0.023 1.762 1.361–2.610 0.047 Sex (Male vs. Female) 0.643 0.312–1.326 0.231 BMI (≥ 24 vs. <24) 1.212 0.578–2.541 0.612 pT stag (Ⅲ-Ⅳ vs. Ⅰ-Ⅱ) 1.168 1.057–2.450 0.031 1.240 0.562–2.737 0.594 pN stage (N + vs. N0) 1.335 1.113–1.829 0.027 1.574 1.097–2.771 0.014 Differention (Poor vs. High/Moderate) 1.052 0.500-2.211 0.894 Lymphatic invasion (Yes vs. No) 1.493 1.109–1.886 0.015 1.157 0.521–2.572 0.720 Vascular invasion (Yes vs. No) 0.898 0.408–1.978 0.789 Perineural invasion (Yes vs. No) 0.661 0.307–1.423 0.290 Neoadjuvant chemotherapy (Yes vs. No) 1.410 0.682–2.914 0.354 ICG-LND (Yes vs. No) 0.936 0.425–2.063 0.870 For RFS (Table 5 ), in the univariate analysis, pT stage (III-IV vs. I-II), pN stage (N + vs. N0), and lymphatic invasion (Yes vs. No) were significant. In the multivariate analysis, pT stage (HR = 1.530, 95% CI: 1.026–2.833, P = 0.016) and pN stage (HR = 1.698, 95% CI: 1.278–2.483, P = 0.031) remained significant predictors of recurrence. Again, ICG-LND did not show a significant effect on RFS (HR = 0.879, 95% CI: 0.470–1.641, P = 0.685). Table 5 The Cox regression of RFS for patients Clinicopathological variables RFS Univariate analysis Multivariate analysis HR 95% CI P HR 95% CI P Age (≥ 60 vs. <60) 0.925 0.523–1.636 0.789 Sex (Male vs. Female) 0.674 0.381–1.192 0.175 BMI (≥ 24 vs. <24) 0.968 0.545–1.718 0.910 pT stag (Ⅲ-Ⅳ vs. Ⅰ-Ⅱ) 1.578 1.170–2.862 0.033 1.530 1.026–2.833 0.016 pN stage (N + vs. N0) 1.631 1.036–2.025 0.029 1.698 1.278–2.483 0.031 Differention (Poor vs. High/Moderate) 0.961 0.533–1.732 0.895 Lymphatic invasion (Yes vs. No) 1.582 1.307-2.100 0.046 0.513 0.258–1.020 0.057 Vascular invasion (Yes vs. No) 1.022 0.555–1.882 0.945 Perineural invasion (Yes vs. No) 0.792 0.441–1.424 0.437 Neoadjuvant chemotherapy (Yes vs. No) 0.957 0.542–1.690 0.879 ICG-LND (Yes vs. No) 0.879 0.470–1.641 0.685 Discussion Lateral lymph node dissection (LLND) is a cornerstone of surgical management for locally advanced mid-to-lower rectal cancer, particularly for patients at high risk of lateral lymph node metastasis, the impact of ICG on long-term oncological outcomes of rectal cancer after LLND remains a subject of debate [ 15 – 18 ] . This study aimed to evaluate whether integrating indocyanine green (ICG)-guided LLND into standard practice could enhance long-term prognostic outcomes, including overall survival (OS), recurrence-free survival (RFS), and patterns of clinical failure. The findings provide valuable insights into the potential of ICG to optimize surgical precision while also highlighting its limitations in terms of oncological efficacy. Our results showed that ICG-guided LLND significantly increased the total number of harvested lymph nodes, supporting previous findings that ICG enhances lymphatic mapping through real-time fluorescence imaging [ 18 – 22 ] . This improved visualization may contribute to more comprehensive lymphadenectomy, aiding in accurate staging and potentially reducing residual disease. However, despite these advantages, no significant difference was observed in the number of harvested or positive lateral lymph nodes between the groups (P = 0.611, P = 0.455), consistent with previous studies [ 23 ] . This suggests that while ICG improves overall lymph node retrieval, its impact on lateral lymph node dissection may be limited, possibly due to anatomical complexity or variations in tracer distribution. Further research is needed to explore optimization strategies for ICG application in LLND. Postoperative recovery metrics in the ICG-LND group showed some advantages. A shorter median hospital stay was observed, which may be attributed to reduced surgical trauma facilitated by the enhanced precision of ICG-guided dissection. These findings are consistent with studies suggesting that fluorescence guidance minimizes unnecessary tissue damage and optimizes the efficiency of lymph node clearance [ 24 – 26 ] . However, operative time and estimated blood loss were similar between the groups, suggesting that the procedural complexity and overall surgical risks remain largely unaffected. Importantly, complication rates, including intraoperative bleeding, anastomotic leakage, and infections, were low and comparable between the groups, supporting the safety and feasibility of ICG-guided procedures in clinical practice. Kaplan-Meier survival analyses revealed no significant differences between the ICG-LND and control groups in OS, RFS, or LR rates during follow-up period. Both groups demonstrated high survival rates at the 3-year mark, with comparable outcomes. The Cox regression analyses further supported these findings, as ICG-LND showed no significant impact on OS or RFS. These results suggest that while ICG enhances surgical precision, it does not confer significant advantages in oncological outcomes. The low rates of local and distant recurrence observed across the cohort emphasize the importance of meticulous surgical technique in achieving successful outcomes. These findings are consistent with reports from high-volume centers, which indicate that standardized lateral lymph node dissection (LLND) protocols can provide excellent locoregional control, regardless of adjunctive measures such as ICG. [ 22 , 27 ] . The versatility of ICG extends beyond LLND, with established applications in colorectal cancer surgery, such as assessing bowel perfusion during anastomosis, identifying sentinel lymph nodes, and mapping lymphatic drainage. These applications have demonstrated significant potential in reducing surgical complications and improving perioperative outcomes [ 22 , 28 – 30 ] . However, in the specific context of LLND, the findings of this study indicate that the impact of ICG on long-term oncological outcomes is modest. This aligns with studies reporting that while ICG improves intraoperative visualization, its direct influence on survival or recurrence rates may be limited. Nevertheless, the reduction in surgical variability and the potential for facilitating learning curves in less experienced surgeons highlight its value as an adjunctive tool. The adoption of ICG in colorectal cancer surgery varies widely across regions. In Japan and other Asian countries where LLND is routinely performed, studies have reported that ICG enhances lymph node clearance and may improve outcomes in specific patient subgroups [ 18 , 30 ] . In contrast, Western countries, where LLND is less commonly practiced, remain skeptical about the cost-effectiveness of ICG, particularly in the absence of robust evidence linking its use to improved survival outcomes. This regional disparity underscores the need for standardized protocols and further research to clarify the role of ICG in diverse clinical settings. Several challenges limit the broader adoption of ICG-guided LLND. Although a sample size calculation was conducted in this study, the high survival rates observed within the study population raise concerns about potential underpowering. Given the possibility of small, yet clinically significant differences being overlooked, the study may have lacked sufficient statistical power to detect subtle treatment effects. This limitation could affect the accuracy and generalizability of the findings. To address this issue, future studies should consider increasing the sample size or employing alternative methodologies to ensure robust statistical power, thereby enabling a more comprehensive and reliable assessment of treatment outcomes.. Moreover, the retrospective nature of this study, introduces inherent biases that could influence the findings. A longer follow-up period may be necessary to capture late recurrences or survival differences, emphasizing the importance of prospective, multicenter trials. At last, this male-dominated population in this study, with narrower pelvic anatomies, may complicate pelvic dissection, especially for mid- to low-rectal tumors. The use of rigid laparoscopic instruments in confined spaces could impact operating time and specimen quality. While robotic systems, such as the Da Vinci system with FireFly mode, can address many of these challenges [ 31 , 32 ] , further research is needed to compare laparoscopic and robotic LLND in rectal cancer patients to better assess the advantages of robotic surgery. Despite these challenges, ICG’s integration with emerging technologies such as artificial intelligence and molecular imaging represents an exciting avenue for future research. Artificial intelligence could enhance the detection of micro-metastases and refine surgical strategies by integrating fluorescence imaging data with preoperative imaging and clinical parameters [ 33 , 34 ] . Cost-effectiveness analyses will also be critical, particularly in resource-limited settings where the widespread adoption of ICG remains challenging. Additionally, standardizing the protocols for ICG injection and fluorescence imaging could further optimize its utility in clinical practice. In conclusion, this study provides valuable evidence on the use of ICG-guided LLND in mid-to-lower rectal cancer. While ICG improves intraoperative visualization and facilitates lymph node dissection, its impact on long-term oncological outcomes, including survival and recurrence rates, appears limited. These findings emphasize the need for rigorous prospective trials to validate the prognostic value of ICG in colorectal cancer surgery. Until such evidence emerges, ICG should be regarded as a complementary tool for enhancing surgical precision rather than a transformative technique for improving survival outcomes. Declarations Ethics approval and consent to participate The research protocol received approval from the Ethics Advisory Committee of the Chinese Academy of Medical Sciences Cancer Hospital, as well as from the institutional review boards of each participating center. Given the retrospective design of the study, written informed consent was not required, and an opt-out method was employed to disclose study details. This research was in compliance with the Helsinki Declaration. Consent for publication All authors have approved the final version of the article and agree the submission. This article didn’t present images or other personal or clinical details of participants. Availability of data and materials The datasets used and/or analysed during the current study are available from the corresponding author on reasonable request. Competing Interests The authors declare no conflict of interest. Funding This research was funded by the National Key Research and Development Program (No. 2022YFC2505003), CAMS Innovation Fund for Medical Sciences (No. 2022-12M-C&T-B-057). Authors' contributions Wenlong Qiu: Conceptualization, Methodology, Formal analysis, investigation, Writing - original draft. Yu Liu: Resources, Data curation, Writing - review & editing. Shiwen Mei: Resources, Data curation, Writing - review & editing. Yuegang Li: Resources, Data curation, Writing - review & editing. Jichuan Quan: Resources, Data curation, Writing - review & editing. Qian Liu: Conceptualization, Methodology, Writing - review & editing, Supervision, Project administration. Acknowledgments The authors would like to thank the patients who participated in this study. 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Combined laparoscopic lymphoadenectomy of lateral pelvic and inguinal nodal metastases using indocyanine green fluorescence imaging guidance in low rectal cancer after preoperative chemoradiotherapy: a case report. BMC Gastroenterol. 2022;22(1):123. Yoo RN, Cho HM, Kye BH, Lee YS, Kim YS. Reappraisal of the Lymphatic Drainage System of the Distal Rectum: Functional Lymphatic Flow into the Presacral Space and Its Clinical Implication in Rectal Cancer Treatment. Biomedicines 2023, 11(2). Watanabe J, Ohya H, Sakai J, Suwa Y, Goto K, Nakagawa K, et al. Long-term outcomes of indocyanine green fluorescence imaging-guided laparoscopic lateral pelvic lymph node dissection for clinical stage II/III middle-lower rectal cancer: a propensity score-matched cohort study. Tech Coloproctol. 2023;27(9):759–67. Ryu S, Hara K, Kitagawa T, Okamoto A, Marukuchi R, Ito R, et al. Fluorescence vessel and ureter navigation during laparoscopic lateral lymph node dissection. Langenbecks Arch Surg. 2022;407(1):305–12. Dai JY, Han ZJ, Wang JD, Liu BS, Liu JY, Wang YC. Short-term outcomes of near-infrared imaging using indocyanine green in laparoscopic lateral pelvic lymph node dissection for middle-lower rectal cancer: A propensity score-matched cohort analysis. Front Med (Lausanne). 2022;9:1039928. Su H, Xu Z, Bao M, Luo S, Liang J, Pei W, et al. Lateral pelvic sentinel lymph node biopsy using indocyanine green fluorescence navigation: can it be a powerful supplement tool for predicting the status of lateral pelvic lymph nodes in advanced lower rectal cancer. Surg Endosc. 2023;37(5):4088–96. Wu CY, Zhong WJ, Ye K. Preliminary study of indocyanine green-guided laparoscopic lateral lymph node dissection for rectal cancer. PLoS ONE. 2024;19(7):e0307077. Kim HJ, Choi G-S, Park JS, Park SY, Cho SH, Seo AN et al. S122: impact of fluorescence and 3D images to completeness of lateral pelvic node dissection. Surg Endosc, 34(1): 469–76. Zhou S-C, Tian Y-T, Wang X-W, Zhao C-D, Ma S, Jiang J et al. Application of indocyanine green-enhanced near-infrared fluorescence-g uided imaging in laparoscopic lateral pelvic lymph node dissection for middle-low rectal cancer. World J Gastroenterol, 25(31): 4502–11. Kawada K, Yoshitomi M, Inamoto S, Sakai Y. Indocyanine Green Fluorescence-Guided Laparoscopic Lateral Lymph Node Dissection for Rectal Cancer. Dis Colon Rectum, 62(11): 1401. Watanabe J, Ohya H, Sakai J, Suwa Y, Goto K, Nakagawa K et al. Long-term outcomes of indocyanine green fluorescence imaging-guided la paroscopic lateral pelvic lymph node dissection for clinical stage II/ III middle-lower rectal cancer: a propensity score-matched cohort stud y. Tech Coloproctol, 27(9): 759–67. Soran A, Senol K, Lupinacci K. Navigating Lymphedema: The Impact of Indocyanine Green Lymphography on Personalized Therapy Outcomes in Breast Cancer Patients. Clin Breast Cancer: S1526-8209(1524)00288-X. Shevchenko I, Serban D, Dascalu AM, Tribus L, Alius C, Cristea BM et al. Factors Affecting the Efficiency of Near-Infrared Indocyanine Green (N IR/ICG) in Lymphatic Mapping for Colorectal Cancer: A Systematic Revie w. Cureus, 16(2): e55290. Son GM, Yun MS, Lee IY, Im SB, Kim KH, Park SB et al. Clinical Effectiveness of Fluorescence Lymph Node Mapping Using ICG fo r Laparoscopic Right Hemicolectomy: A Prospective Case-Control Study. Cancers (Basel), 15(20): 4927. Sueda T, Yasui M, Nishimura J, Kagawa Y, Kitakaze M, Mori R et al. Prognostic impact of lateral sentinel lymph node biopsy using indocyan ine green on oncological outcomes for clinical stage II/III lower rect al cancer without suspected lateral lymph node metastasis. Langenbecks Arch Surg, 409(1): 311. Kehagias D, Lampropoulos C, Bellou A, Kehagias I. The use of indocyanine green for lateral lymph node dissection in rect al cancer-preliminary data from an emerging procedure: a systematic re view of the literature. Tech Coloproctol, 28(1): 53. Lim MGL, Lopez MPJ, Onglao MAS, Monroy HJ 3rd, Sacdalan MDP. Indocyanine Green (ICG) Fluorescence in the Assessment of Vascularity of Anastomotic Margins in Colorectal Surgery in a Lower Middle-Income Country (LMIC) Hospital. Acta Med Philipp, 58(16): 8–13. Sun Y, Tang Z, Xu Z, Chen Z, Huang S, Wang X et al. Indocyanine green near-infrared fluorescence-assisted video endoscopic inguinal lymph node dissection for rectal cancer: a single-center exp erience. Tech Coloproctol, 28(1): 64. Dai J-Y, Han Z-J, Wang J-D, Liu B-S, Liu J-Y, Wang Y-C. Short-term outcomes of near-infrared imaging using indocyanine green i n laparoscopic lateral pelvic lymph node dissection for middle-lower r ectal cancer: A propensity score-matched cohort analysis. Front Med (Lausanne), 9: 1039928. Guo H, Luo Y, Fu Z, Wang D. Indocyanine green fluorescence imaging for lymph node detection and lo ng-term clinical outcomes in colorectal cancer surgery: A systematic r eview and meta-analysis. World J Surg: 10.1002/wjs.12412 Cassinotti E, Costa S, De Pascale S, Oreggia B, Palazzini G, Boni L. How to reduce surgical complications in rectal cancer surgery using fl uorescence techniques. Minerva Chir, 73(2): 210–6. Gröne J, Koch D, Kreis ME. Impact of intraoperative microperfusion assessment with Pinpoint Perfu sion Imaging on surgical management of laparoscopic low rectal and ano rectal anastomoses. Colorectal Dis, 17 Suppl 3: 22–8. Jafari MD, Lee KH, Halabi WJ, Mills SD, Carmichael JC, Stamos MJ et al. The use of indocyanine green fluorescence to assess anastomotic perfus ion during robotic assisted laparoscopic rectal surgery. Surg Endosc, 27(8): 3003–8. Aliyev V, Piozzi GN, Huseynov E, Mustafayev TZ, Kayku V, Goksel S et al. Robotic male and laparoscopic female sphincter-preserving total mesore ctal excision of mid-low rectal cancer share similar specimen quality, complication rates and long-term oncological outcomes. J Robot Surg, 17(4): 1637–44. Aliyev V, Goksel S, Bakir B, Guven K, Asoglu O. Sphincter-Saving Robotic Total Mesorectal Excision Provides Better Mes orectal Specimen and Good Oncological Local Control Compared with Lapa roscopic Total Mesorectal Excision in Male Patients with Mid-Low Recta l Cancer. Surg Technol Int, 38: 160–6. Lim ZY, Mohan S, Balasubramaniam S, Ahmed S, Siew CCH, Shelat VG. Indocyanine green dye and its application in gastrointestinal surgery: The future is bright green. World J Gastrointest Surg, 15(9): 1841–57. Ma Z, Wang F, Wang W, Zhong Y, Dai H. Deep learning for in vivo near-infrared imaging. Proc Natl Acad Sci U S A, 118(1): e2021446118. Additional Declarations No competing interests reported. Cite Share Download PDF Status: Under Review Version 1 posted Editorial decision: Revision requested 22 Apr, 2025 Editor assigned by journal 22 Apr, 2025 Reviews received at journal 21 Apr, 2025 Reviews received at journal 12 Apr, 2025 Reviewers agreed at journal 11 Apr, 2025 Reviewers agreed at journal 11 Apr, 2025 Reviewers invited by journal 11 Apr, 2025 Submission checks completed at journal 11 Apr, 2025 First submitted to journal 31 Mar, 2025 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-5570995","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":442376349,"identity":"6c181c31-7ec5-4146-ae6a-74043804e6bb","order_by":0,"name":"Wenlong Qiu","email":"","orcid":"","institution":"National Cancer Center, Chinese Academy of Medical Sciences and Peking Union Medical College","correspondingAuthor":false,"prefix":"","firstName":"Wenlong","middleName":"","lastName":"Qiu","suffix":""},{"id":442376352,"identity":"b34ebe10-0d52-4b2a-bb52-0bcdb61c930c","order_by":1,"name":"Yu Liu","email":"","orcid":"","institution":"National Cancer Center, Chinese Academy of Medical Sciences and Peking Union Medical College","correspondingAuthor":false,"prefix":"","firstName":"Yu","middleName":"","lastName":"Liu","suffix":""},{"id":442376356,"identity":"ac7a6221-1c30-4ded-93a8-b70452739b23","order_by":2,"name":"Shiwen Mei","email":"","orcid":"","institution":"National Cancer Center, Chinese Academy of Medical Sciences and Peking Union Medical College","correspondingAuthor":false,"prefix":"","firstName":"Shiwen","middleName":"","lastName":"Mei","suffix":""},{"id":442376358,"identity":"3a5333bf-cc83-47ed-8b2b-ae72b24f4ac9","order_by":3,"name":"Jichuan Quan","email":"","orcid":"","institution":"National Cancer Center, Chinese Academy of Medical Sciences and Peking Union Medical College","correspondingAuthor":false,"prefix":"","firstName":"Jichuan","middleName":"","lastName":"Quan","suffix":""},{"id":442376360,"identity":"f5fc21d2-263e-4704-8497-94f11c9f1035","order_by":4,"name":"Yuegang Li","email":"","orcid":"","institution":"National Cancer Center, Chinese Academy of Medical Sciences and Peking Union Medical College","correspondingAuthor":false,"prefix":"","firstName":"Yuegang","middleName":"","lastName":"Li","suffix":""},{"id":442376362,"identity":"9a8fd0e9-9708-4a6c-99e1-661e012af339","order_by":5,"name":"Qian Liu","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAwElEQVRIiWNgGAWjYBACPmYILcfeAKIMLAhrYYNqMeY5ANYiQYQWKJ3YA9bCQIwWdh7D2wU1duk97D2mG34USDDwt3cnEHAYj7H1jGPJuT08x9Ju9gAdJnHm7AZCWsykeRsO5O6XSD52gweoxUAilzgt6TwSiW03/5CiJYEHaMttIm1hK7bmOZZsCPLLbRkDCR6CfuHnP7zxNk+NnTwPe4/ZzTd/bOT423vxawEBlLjgIagcQ8soGAWjYBSMAgwAAIUqOKgJHR6XAAAAAElFTkSuQmCC","orcid":"","institution":"National Cancer Center, Chinese Academy of Medical Sciences and Peking Union Medical College","correspondingAuthor":true,"prefix":"","firstName":"Qian","middleName":"","lastName":"Liu","suffix":""}],"badges":[],"createdAt":"2024-12-03 09:38:42","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-5570995/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-5570995/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":80587414,"identity":"ddb17710-4d13-49cf-b738-2c183fd0732c","added_by":"auto","created_at":"2025-04-15 01:20:47","extension":"jpg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":156261,"visible":true,"origin":"","legend":"\u003cp\u003eFlowchart of patient.\u003c/p\u003e","description":"","filename":"Figure1.jpg","url":"https://assets-eu.researchsquare.com/files/rs-5570995/v1/7b6e829d68366b6cec73d217.jpg"},{"id":80587424,"identity":"643aef67-23ab-418e-8748-342bed20354d","added_by":"auto","created_at":"2025-04-15 01:20:50","extension":"jpg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":1246594,"visible":true,"origin":"","legend":"\u003cp\u003eFluorescence-guided lateral lymph node dissection.\u003c/p\u003e\n\u003cp\u003ea. Opening of the lateral region according to anatomical structure and ICG fluorescence guidance\u003c/p\u003e\n\u003cp\u003eb. Dissection of the lateral obturator lymph nodes\u003c/p\u003e\n\u003cp\u003ec. Removal of the lateral internal iliac lymph nodes\u003c/p\u003e\n\u003cp\u003ed. Lateral region after lymph node dissection under ICG fluorescence\u003c/p\u003e","description":"","filename":"Figure2.jpg","url":"https://assets-eu.researchsquare.com/files/rs-5570995/v1/27af5597c81e70978dcea505.jpg"},{"id":80587418,"identity":"44c3ab48-2575-4f2b-901b-b2dbac60e76a","added_by":"auto","created_at":"2025-04-15 01:20:48","extension":"jpg","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":1227676,"visible":true,"origin":"","legend":"\u003cp\u003eKaplan–Meier curve for clinical outcome.\u003c/p\u003e\n\u003cp\u003ea. Overall survival. Kaplan–Meier curve for the comparison of the overall survival. ICG-LND, indocyanine green lymph node dissection.\u003c/p\u003e\n\u003cp\u003eb. Recurrence free survival. Kaplan–Meier curve for the comparison of the recurrence-free survival.\u003c/p\u003e\n\u003cp\u003ec. Cumulative local recurrence rate. Kaplan–Meier curve for the comparison of the cumulative local recurrence rate.\u003c/p\u003e\n\u003cp\u003ed. Cumulative distant metastatic rate. Kaplan–Meier curve for the comparison of the cumulative distant metastatic rate.\u003c/p\u003e","description":"","filename":"Figure3.jpg","url":"https://assets-eu.researchsquare.com/files/rs-5570995/v1/7bc4193ae1648962478cdede.jpg"},{"id":80588152,"identity":"c9f38292-923a-4034-8971-f0899bf55ca4","added_by":"auto","created_at":"2025-04-15 01:36:48","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":3553407,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-5570995/v1/d4281187-38b5-455e-96c9-65b1180bb683.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"The Short and Long Oncological Outcome of Indocyanine Green for Lateral Lymph Node Dissection in Mid-low Rectum Cancer","fulltext":[{"header":"Introduction","content":"\u003cp\u003eLateral lymph node dissection (LLND) is a crucial component of the surgical treatment for local advanced colorectal cancer, particularly in patients at high risk of lateral lymph node metastasis. Accurate identification and thorough dissection of these nodes are vital to achieving optimal oncological outcomes. Failure to address lateral lymph node metastasis appropriately can lead to increased local recurrence rates and compromised survival\u003csup\u003e[\u003cspan additionalcitationids=\"CR2\" citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]\u003c/sup\u003e. The introduction of indocyanine green (ICG), a near-infrared fluorescent dye, has been hailed as a significant advancement in enhancing the accuracy and effectiveness of LLND. By enabling real-time, intraoperative visualization of lymphatic structures and blood flow, ICG may facilitate more comprehensive lymph node clearance and reduce postoperative complications, such as anastomotic leakage\u003csup\u003e[\u003cspan additionalcitationids=\"CR5\" citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eThe utility of ICG in colorectal cancer surgery extends beyond LLND. It has been used in evaluating bowel perfusion during anastomosis, identifying sentinel lymph nodes, and mapping lymphatic drainage, all of which are crucial for improving surgical outcomes \u003csup\u003e[\u003cspan additionalcitationids=\"CR8\" citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]\u003c/sup\u003e. The use of ICG in LLND specifically has shown promise in improving the detection and excision of metastatic lymph nodes that might otherwise be missed by conventional methods. By enhancing the precision of nodal dissection, ICG is hypothesized to contribute to better long-term outcomes, such as reducing local recurrence rates and improving overall survival. However, the actual impact of ICG-guided LLND on colorectal cancer prognosis remains a topic of ongoing international debate.\u003c/p\u003e \u003cp\u003eGlobally, a growing body of evidence supports the use of ICG in colorectal cancer surgery. A study from Japan suggests that ICG may enhance the quality of laparoscopic LPLND and improve local control of the lateral pelvis, leading to better postoperative outcomes \u003csup\u003e[\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e, \u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]\u003c/sup\u003e. However, this study did not elaborate on the impact of ICG on the short-term oncological outcomes of rectal cancer patients undergoing LLND, such as the number of retrieved lymph nodes, intraoperative blood loss, postoperative complications, and hospital stay. Additionally, the sample size was relatively small (n\u0026thinsp;=\u0026thinsp;172).\u003c/p\u003e \u003cp\u003eIn China, the adoption of ICG in colorectal cancer surgery has been met with cautious optimism. Chinese studies have reported that ICG-guided LLND improves lymph node clearance, however, In China, studies have demonstrated the safety and feasibility of ICG in LLND for rectal cancer, particularly in terms of short-term outcomes\u003csup\u003e[\u003cspan additionalcitationids=\"CR13\" citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]\u003c/sup\u003e. However, there is still a lack of sufficient research on its long-term oncological prognosis.\u003c/p\u003e \u003cp\u003eTherefore, our study aims to critically evaluate the role of ICG in LLND, focusing on whether this technique leads to improved oncological outcomes, such as lower recurrence rates and enhanced overall survival, compared to traditional methods. Through a comprehensive analysis of both domestic and international data, we seek to clarify the prognostic value of ICG and contribute to the ongoing debate regarding its efficacy.\u003c/p\u003e"},{"header":"Materials and methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003ePatient Population\u003c/h2\u003e \u003cp\u003eThis retrospective, multi-center study aimed to evaluate the effectiveness of ICG-assisted laparoscopic LLND (ICG-LND) compared to conventional laparoscopic LLND without ICG, using propensity score matching for comparison. The study involved patients who underwent laparoscopic LLND for mid and lower rectal cancer between January 2018 and June 2022 (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). The study period concluded on 30 September 2024, and patients lost to follow-up before this date were censored at their last documented visit, and the median follow-up time was 48.2 months. The research protocol received approval from the Ethics Advisory Committee of the Chinese Academy of Medical Sciences Cancer Hospital, as well as from the institutional review boards of each participating center. Given the retrospective design of the study, written informed consent was not required, and an opt-out method was employed to disclose study details. The study was registered with the Chinese Clinical Trial Registry.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eEligibility Criteria\u003c/h3\u003e\n\u003cp\u003eInclusion criteria for this study were: (1) rectal cancer patients aged 18 or older; (2) histologically confirmed cases of adenocarcinoma; (3) clinical stage I\u0026ndash;III; (4) tumor location within 100 mm from the anal verge (AV); and (5) patients who underwent laparoscopic LLND. Patients were excluded if they: (1) younger than 18 or older than 80 years, (2) were preoperatively diagnosed with distant metastasis at first diagnosis, (3) had undergone total pelvic exenteration, or (4) combined resection with other organs.\u003c/p\u003e\n\u003ch3\u003eFluorescence-Guided Lymph Node Dissection\u003c/h3\u003e\n\u003cp\u003eThree research centers with a long-term collaboration formed a lateral lymph node management consortium. The similar ICG-LND protocols and implemented standardized training was adopted on ICG administration, ensuring procedural consistency and minimizing bias. In the ICG-LND group, indocyanine green (ICG) was administered via submucosal injection. A dose of 0.25 mg/kg of ICG was injected into the submucosal layer around the tumor approximately one hours before surgery to allow for optimal uptake by the local lymphatic system. During surgery, near-infrared (NIR) fluorescence imaging was used to map the lymphatic pathways and highlight lateral lymph nodes. The fluorescent signal enabled surgeons to more accurately identify and dissect lymph nodes, potentially improving the precision and completeness of lymph node clearance (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). During the procedure, a laparoscopic NIR camera system was used to visualize the fluorescent signal from the lymph nodes and surrounding lymphatic vessels.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e\n\u003ch3\u003eSurgical Technique for Lateral Lymph Node Dissection\u003c/h3\u003e\n\u003cp\u003eLateral lymph node dissection (LLND) was performed following a standardized laparoscopic technique by experienced surgeons certified in laparoscopic total mesorectal excision (TME). A 5-port approach was typically employed, with 12 mm trocars placed at the umbilicus and right lower abdomen, and 5 mm trocars placed in the right upper, left upper, and left lower abdomen. Key areas targeted for dissection included the internal pudendal artery and the obturator artery, as these are common sites for pelvic lymph node metastasis and require careful preservation of autonomic nerves.\u003c/p\u003e \u003cp\u003eThe dissection began with the ureteric hypogastric fascia, preserving the ureter and hypogastric nerve as a unified membranous structure. The lymph nodes in the obturator region were then accessed by dissecting the lateral pelvic wall, involving the psoas major and internal obturator muscles. After dividing the medial umbilical ligament, the bladder hypogastric fascia was dissected to remove lymph nodes in the obturator region. Throughout this process, care was taken to preserve the obturator nerve, while the obturator vessels were transected.\u003c/p\u003e \u003cp\u003eDissection continued around the internal iliac and pudendal arteries, extending to the Alcock canal. The internal pudendal artery, along with its subvesical branches, was selectively ligated, and the inferior vesical artery and vein were severed distal to their junction with the bladder, ensuring complete autonomic nerve preservation.\u003c/p\u003e\n\u003ch3\u003eFluorescence-Assisted Lymphatic Mapping\u003c/h3\u003e\n\u003cp\u003eThe ICG-stained lymph nodes, including the internal iliac (No. 263), obturator (No. 283), external iliac (No. 293), and common iliac lymph nodes (No. 273), were identified using the NIR camera system. The fluorescent lymphatic drainage patterns, lymph nodes, and connecting lymphatic vessels were compared to the branching patterns of the iliac vessels to delineate the boundaries for lymph node dissection. The procedure for LLND in patients who received NIR guidance was essentially the same as in those who did not.\u003c/p\u003e \u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003ePostoperative Follow-Up\u003c/h2\u003e \u003cp\u003eAfter discharge, patients were monitored with tumor markers (CEA, CA 19\u0026ndash;9) and CT scans every 3 months for the first 2 years and every 6 months for 3 to 5 years to assess for any recurrence or metastasis.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec9\" class=\"Section2\"\u003e \u003ch2\u003eStatistical Analysis\u003c/h2\u003e \u003cp\u003eThe primary outcomes was overall survival (OS), and the 3-year recurrence free survival (RFS), local recurrence (LR) rate, and distant metastatic (DM) rate were also analyzed. Data were presented as median values with interquartile ranges (IQR). Categorical and continuous variables were compared using Pearson\u0026rsquo;s chi-square test and the Mann\u0026ndash;Whitney U test, respectively. Survival outcomes (OS, RFS, LR, LLR) were evaluated using the Kaplan\u0026ndash;Meier method and the log-rank test. A p-value of less than 0.05 was considered statistically significant, and all analyses were conducted using IBM SPSS Statistics version 23.0 (IBM Corp., Somers, NY, USA).\u003c/p\u003e \u003c/div\u003e"},{"header":"Results","content":"\u003cdiv id=\"Sec11\" class=\"Section2\"\u003e \u003ch2\u003ePatient Characteristics and Tumor Profiles\u003c/h2\u003e \u003cp\u003eAmong the 258 patients included, the ICG-LND group had a significantly younger mean age compared to the control group (56.0\u0026thinsp;\u0026plusmn;\u0026thinsp;10.8 vs. 58.9\u0026thinsp;\u0026plusmn;\u0026thinsp;11.1 years, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.048), while other baseline characteristics, including sex distribution and BMI, showed no significant differences. Clinical tumor (cT) and nodal (cN) statuses were comparable between groups, with advanced cT3\u0026ndash;4 and cN1\u0026ndash;2 predominating in both. Pathologically, the ICG-LND group had a higher proportion of early-stage tumors (pT1\u0026ndash;2: 51.9% vs. 36.9%, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.024) but no differences in nodal status or overall pathologic stage. Poorly differentiated tumors were more frequent in the ICG-LND group (48.1% vs. 32.4%, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.016), while lymphatic, vascular, and perineural invasion rates, as well as tumor size and neoadjuvant chemotherapy use, were similar across groups.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec12\" class=\"Section2\"\u003e \u003ch2\u003eSurgical Outcomes and Postoperative Recovery\u003c/h2\u003e \u003cp\u003eIn the comparison of surgical outcomes between the control group and the ICG-LND group, the median number of harvested lateral lymph nodes was slightly higher in the ICG-LND group (9 [IQR: 5\u0026ndash;13]) compared to the control group (7 [IQR: 4\u0026ndash;13]), but the difference was not statistically significant (P\u0026thinsp;=\u0026thinsp;0.611). Similarly, the number of positive lateral lymph nodes did not differ significantly between groups (P\u0026thinsp;=\u0026thinsp;0.455).\u003c/p\u003e \u003cp\u003eHowever, the ICG-LND group demonstrated a significantly higher total number of harvested lymph nodes (28 [IQR: 23\u0026ndash;37] vs. 26 [IQR: 19\u0026ndash;37], P\u0026thinsp;=\u0026thinsp;0.042), suggesting improved overall lymph node retrieval. Despite this, the number of positive total nodes remained similar between the two groups (P\u0026thinsp;=\u0026thinsp;0.962).\u003c/p\u003e \u003cp\u003eNotably, the postoperative hospital stay was significantly shorter in the ICG-LND group (6 [IQR: 5\u0026ndash;8] days vs. 7 [IQR: 6\u0026ndash;9] days, P\u0026thinsp;\u0026lt;\u0026thinsp;0.001), indicating potential benefits in postoperative recovery. No significant differences were observed between the control group and the ICG-LND group in terms of estimated blood loss (50 mL [20, 60] vs. 30 mL [20, 100], P\u0026thinsp;=\u0026thinsp;0.765), operating time (240 minutes [200, 305] vs. 251 minutes [200, 290], P\u0026thinsp;=\u0026thinsp;0.523), or complication rates (P\u0026thinsp;=\u0026thinsp;0.871). Specifically, the complication rates included intraoperative bleeding (4 vs. 2), anastomotic leakage (7 vs. 3), ileus (3 vs. 1), and incisional infection (3 vs. 1) for the control and ICG-LND groups, respectively.\u003c/p\u003e \u003cp\u003eThese findings suggest that while ICG-LND does not significantly increase lateral lymph node retrieval, it may contribute to enhanced overall lymph node dissection and improved postoperative recovery.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec13\" class=\"Section2\"\u003e \u003ch2\u003ePatterns of Clinical Failure\u003c/h2\u003e \u003cp\u003eIn the cohort, there were no significant differences in patterns of distant metastasis between the control and ICG-LND groups. Lung metastases were observed in 17 patients (9.5%) in the control group and 7 patients (8.9%) in the ICG-LND group (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.871), while liver metastases occurred in 9 (5.0%) and 4 (5.1%) patients, respectively (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.767).\u003c/p\u003e \u003cp\u003eLocal recurrence patterns were also comparable between the groups. Anastomotic recurrence occurred in 4 patients (2.2%) in the control group and 1 patient (1.3%) in the ICG-LND group (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.976). Central pelvic recurrence was slightly higher in the control group (17 [9.5%] vs. 4 [5.1%], \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.230), and lateral pelvic recurrence was noted in 7 (3.9%) and 2 (2.5%) patients, respectively (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.851).\u003c/p\u003e \u003cp\u003eNo significant differences in clinical failure patterns were observed between the two groups across all evaluated parameters.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec14\" class=\"Section2\"\u003e \u003ch2\u003eKaplan-Meier Survival Analysis and Recurrence Rates\u003c/h2\u003e \u003cp\u003eThe Kaplan-Meier survival analyses (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e) revealed no significant differences between the ICG-LND group (n\u0026thinsp;=\u0026thinsp;79) and the control group (n\u0026thinsp;=\u0026thinsp;179) over a 60-month follow-up period for overall survival (P\u0026thinsp;=\u0026thinsp;0.884), recurrence-free survival (P\u0026thinsp;=\u0026thinsp;0.789), or local recurrence rates (P\u0026thinsp;=\u0026thinsp;0.822). At the 3-year mark, the overall survival rates were 92.4% for the ICG-LND group and 93.2% for the control group, while the recurrence-free survival rates were 88.1% and 89.6%, respectively. Both groups demonstrated closely aligned survival curves and comparable local recurrence rates, suggesting that the application of ICG in lymph node dissection does not adversely affect these outcomes.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eFurthermore, the longitudinal data analysis, including the 3-year recurrence rates, showed no significant differences in either local or distant metastatic recurrence between the two groups, with the cumulative recurrence rates remaining low (local recurrence: 6.3% in the ICG-LND group vs. 6.7% in the control group; distant metastasis: 10.1% vs. 10.8%). These consistent findings across multiple survival and recurrence endpoints indicate that ICG-guided lymph node dissection does not improve local control rates or survival outcomes, highlighting its lack of impact on long-term oncological prognosis.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec15\" class=\"Section2\"\u003e \u003ch2\u003eThe results of the Cox regression analyses\u003c/h2\u003e \u003cp\u003eIn the univariate analysis for OS (Table\u0026nbsp;\u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e4\u003c/span\u003e), factors such as age (\u0026ge;\u0026thinsp;60 years), pN stage (N\u0026thinsp;+\u0026thinsp;vs. N0), and lymphatic invasion (Yes vs. No) were found to be significant. However, when adjusting for potential confounders in the multivariate analysis, only age (HR\u0026thinsp;=\u0026thinsp;1.762, 95% CI: 1.361\u0026ndash;2.610, P\u0026thinsp;=\u0026thinsp;0.047) and pN stage (HR\u0026thinsp;=\u0026thinsp;1.574, 95% CI: 1.097\u0026ndash;2.771, P\u0026thinsp;=\u0026thinsp;0.014) remained significant. Interestingly, ICG-guided lymph node dissection (ICG-LND) did not show a significant effect on OS (HR\u0026thinsp;=\u0026thinsp;0.936, 95% CI: 0.425\u0026ndash;2.063, P\u0026thinsp;=\u0026thinsp;0.870).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003ePatient characteristics.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"5\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVariable\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eTotal (n, %)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eControl (n, %)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eICG-LND (n, %)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eP\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;179)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;79)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge, yr (Mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e56.0\u0026thinsp;\u0026plusmn;\u0026thinsp;10.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e58.9\u0026thinsp;\u0026plusmn;\u0026thinsp;11.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.048\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;60\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e143 (55.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e103 (57.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e40 (50.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.303\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026ge;\u0026thinsp;60\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e115 (44.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e76 (42.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e39 (49.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSex\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.461\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFemale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e112 (43.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e75 (41.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e37 (46.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e146 (56.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e104 (58.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e42 (53.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBMI (kg/m2, Mean\u0026thinsp;\u003cem\u003e\u0026plusmn;\u003c/em\u003e\u0026thinsp;SD)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e24.6\u0026thinsp;\u0026plusmn;\u0026thinsp;3.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e23.8\u0026thinsp;\u0026plusmn;\u0026thinsp;3.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.090\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;24\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e109 (42.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e73 (40.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e36 (45.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.473\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026ge;\u0026thinsp;24\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e149 (57.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e106 (59.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e43 (54.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ecT status\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.168\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ecT 1\u0026ndash;2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e65 (25.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e35 (19.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e30 (.38.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ecT 3\u0026ndash;4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e193 (74.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e144 (80.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e49 (62.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ecN status\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.558\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ecN 0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e88 (34.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e59 (33.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e29 (36.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ecN 1\u0026ndash;2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e170 (65.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e120 (67.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e50 (63.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003epT status\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.024\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003epT 1\u0026ndash;2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e107 (41.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e66 (36.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e41 (51.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003epT 3\u0026ndash;4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e151 (58.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e113 (63.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e38 (48.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003epN status\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.385\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003epN 0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e104 (40.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e69 (38.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e35 (44.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003epN 1\u0026ndash;2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e154 (59.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e110 (61.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e44 (55.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNeoadjuvant chmotherapy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.376\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e125 (48.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e90 (50.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e35 (44.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e133 (51.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e89 (49.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e44 (55.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePathologic stage\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.473\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eI-II\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e109 (42.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e73 (40.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e36 (45.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIII\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e149 (57.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e106 (59.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e43 (54.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTumor size (cm, Mean\u0026thinsp;\u003cem\u003e\u0026plusmn;\u003c/em\u003e\u0026thinsp;SD)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4.0\u0026thinsp;\u0026plusmn;\u0026thinsp;1.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e4.1\u0026thinsp;\u0026plusmn;\u0026thinsp;1.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.624\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026le;\u0026thinsp;4.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e157 (60.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e111 (62.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e46 (58.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.566\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026gt;\u0026thinsp;4.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e101 (39.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e68 (38.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e33 (41.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDifferentiation\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.016\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eWell/Moderate\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e162 (62.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e121 (67.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e41 (51.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePoorly\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e96 (37.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e58 (32.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e38 (48.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLymphatic invasion\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.384\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNegative\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e170 (65.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e121 (67.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e49 (62.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePositive\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e88 (34.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e58 (32.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e30 (38.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVascular invasion\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.222\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNegative\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e177 (68.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e127 (70.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e50 (63.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePositive\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e81 (31.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e52 (29.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e29 (36.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePerineural invasion\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.182\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNegative\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e153 (59.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e111 (62.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e42 (53.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePositive\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e105 (40.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e68 (38.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e37 (46.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eThe surgical outcom of control group and ICG-LND group (n\u0026thinsp;=\u0026thinsp;258).\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVariants\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eControl (n\u0026thinsp;=\u0026thinsp;179)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eICG-LND (n\u0026thinsp;=\u0026thinsp;79)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eP\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNumber of harvested lateral lymph nodes, median (IQR)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e7 (4,13)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e9 (5,13)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.611\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNumber of positive lateral lymph nodes, median (IQR)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0 (0,0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0 (0,1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.455\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNumber of harvested total nodes, median (IQR)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e26 (19,37)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e28 (23,37)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.042\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNumber of positive harvested total nodes, median (IQR)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1 (0,4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1 (0,3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.962\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePostoperative hospital stay (day), median (IQR)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e7 (6,9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e6 (5,8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eEstimated blood loss (ml), median (IQR)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e50 (20,60)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e30 (20,100)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.765\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOperating time (min), median (IQR)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e240 (200,305)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e251 (200,290)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.523\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eComplications\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.871\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eintraoperative bleeding\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eanastomotic leakage\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eileus\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eincisional infection\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003ePatterns of clinical failure.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVariants\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eControl (n\u0026thinsp;=\u0026thinsp;179)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eICG-LND (n\u0026thinsp;=\u0026thinsp;79)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eP\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDistant metastasis\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLung\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e17\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.871\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLiver\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.767\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLocal recurrence\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAnastomotic\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.976\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCentral pelvis\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e17\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.230\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLateral pelvis\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.851\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab4\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 4\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eThe Cox regression of OS for patients\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"7\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eClinicopathological variables\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"6\" nameend=\"c7\" namest=\"c2\"\u003e \u003cp\u003eOS\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colspan=\"3\" nameend=\"c4\" namest=\"c2\"\u003e \u003cp\u003eUnivariate analysis\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"3\" nameend=\"c7\" namest=\"c5\"\u003e \u003cp\u003eMultivariate analysis\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eHR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e95% CI\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eP\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eHR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e95% CI\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eP\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge (\u0026ge;\u0026thinsp;60 vs. \u0026lt;60)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.168\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.078\u0026ndash;2.101\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.023\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1.762\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e1.361\u0026ndash;2.610\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.047\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSex (Male vs. Female)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.643\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.312\u0026ndash;1.326\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.231\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBMI (\u0026ge;\u0026thinsp;24 vs. \u0026lt;24)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.212\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.578\u0026ndash;2.541\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.612\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003epT stag (Ⅲ-Ⅳ vs. Ⅰ-Ⅱ)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.168\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.057\u0026ndash;2.450\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.031\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1.240\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.562\u0026ndash;2.737\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.594\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003epN stage (N\u0026thinsp;+\u0026thinsp;vs. N0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.335\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.113\u0026ndash;1.829\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.027\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1.574\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e1.097\u0026ndash;2.771\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.014\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDifferention (Poor vs. High/Moderate)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.052\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.500-2.211\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.894\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLymphatic invasion (Yes vs. No)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.493\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.109\u0026ndash;1.886\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.015\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1.157\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.521\u0026ndash;2.572\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.720\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVascular invasion (Yes vs. No)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.898\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.408\u0026ndash;1.978\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.789\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePerineural invasion (Yes vs. No)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.661\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.307\u0026ndash;1.423\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.290\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNeoadjuvant chemotherapy (Yes vs. No)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.410\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.682\u0026ndash;2.914\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.354\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eICG-LND (Yes vs. No)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.936\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.425\u0026ndash;2.063\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.870\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eFor RFS (Table\u0026nbsp;\u003cspan refid=\"Tab5\" class=\"InternalRef\"\u003e5\u003c/span\u003e), in the univariate analysis, pT stage (III-IV vs. I-II), pN stage (N\u0026thinsp;+\u0026thinsp;vs. N0), and lymphatic invasion (Yes vs. No) were significant. In the multivariate analysis, pT stage (HR\u0026thinsp;=\u0026thinsp;1.530, 95% CI: 1.026\u0026ndash;2.833, P\u0026thinsp;=\u0026thinsp;0.016) and pN stage (HR\u0026thinsp;=\u0026thinsp;1.698, 95% CI: 1.278\u0026ndash;2.483, P\u0026thinsp;=\u0026thinsp;0.031) remained significant predictors of recurrence. Again, ICG-LND did not show a significant effect on RFS (HR\u0026thinsp;=\u0026thinsp;0.879, 95% CI: 0.470\u0026ndash;1.641, P\u0026thinsp;=\u0026thinsp;0.685).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab5\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 5\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eThe Cox regression of RFS for patients\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"7\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eClinicopathological variables\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"6\" nameend=\"c7\" namest=\"c2\"\u003e \u003cp\u003eRFS\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colspan=\"3\" nameend=\"c4\" namest=\"c2\"\u003e \u003cp\u003eUnivariate analysis\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"3\" nameend=\"c7\" namest=\"c5\"\u003e \u003cp\u003eMultivariate analysis\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eHR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e95% CI\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eP\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eHR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e95% CI\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eP\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge (\u0026ge;\u0026thinsp;60 vs. \u0026lt;60)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.925\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.523\u0026ndash;1.636\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.789\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSex (Male vs. Female)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.674\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.381\u0026ndash;1.192\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.175\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBMI (\u0026ge;\u0026thinsp;24 vs. \u0026lt;24)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.968\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.545\u0026ndash;1.718\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.910\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003epT stag (Ⅲ-Ⅳ vs. Ⅰ-Ⅱ)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.578\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.170\u0026ndash;2.862\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.033\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1.530\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e1.026\u0026ndash;2.833\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.016\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003epN stage (N\u0026thinsp;+\u0026thinsp;vs. N0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.631\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.036\u0026ndash;2.025\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.029\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1.698\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e1.278\u0026ndash;2.483\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.031\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDifferention (Poor vs. High/Moderate)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.961\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.533\u0026ndash;1.732\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.895\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLymphatic invasion (Yes vs. No)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.582\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.307-2.100\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.046\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.513\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.258\u0026ndash;1.020\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.057\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVascular invasion (Yes vs. No)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.022\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.555\u0026ndash;1.882\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.945\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePerineural invasion (Yes vs. No)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.792\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.441\u0026ndash;1.424\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.437\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNeoadjuvant chemotherapy (Yes vs. No)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.957\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.542\u0026ndash;1.690\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.879\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eICG-LND (Yes vs. No)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.879\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.470\u0026ndash;1.641\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.685\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e"},{"header":"Discussion","content":"\u003cp\u003eLateral lymph node dissection (LLND) is a cornerstone of surgical management for locally advanced mid-to-lower rectal cancer, particularly for patients at high risk of lateral lymph node metastasis, the impact of ICG on long-term oncological outcomes of rectal cancer after LLND remains a subject of debate \u003csup\u003e[\u003cspan additionalcitationids=\"CR16 CR17\" citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e]\u003c/sup\u003e. This study aimed to evaluate whether integrating indocyanine green (ICG)-guided LLND into standard practice could enhance long-term prognostic outcomes, including overall survival (OS), recurrence-free survival (RFS), and patterns of clinical failure. The findings provide valuable insights into the potential of ICG to optimize surgical precision while also highlighting its limitations in terms of oncological efficacy.\u003c/p\u003e \u003cp\u003eOur results showed that ICG-guided LLND significantly increased the total number of harvested lymph nodes, supporting previous findings that ICG enhances lymphatic mapping through real-time fluorescence imaging \u003csup\u003e[\u003cspan additionalcitationids=\"CR19 CR20 CR21\" citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e]\u003c/sup\u003e. This improved visualization may contribute to more comprehensive lymphadenectomy, aiding in accurate staging and potentially reducing residual disease.\u003c/p\u003e \u003cp\u003eHowever, despite these advantages, no significant difference was observed in the number of harvested or positive lateral lymph nodes between the groups (P\u0026thinsp;=\u0026thinsp;0.611, P\u0026thinsp;=\u0026thinsp;0.455), consistent with previous studies \u003csup\u003e[\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e]\u003c/sup\u003e. This suggests that while ICG improves overall lymph node retrieval, its impact on lateral lymph node dissection may be limited, possibly due to anatomical complexity or variations in tracer distribution. Further research is needed to explore optimization strategies for ICG application in LLND.\u003c/p\u003e \u003cp\u003ePostoperative recovery metrics in the ICG-LND group showed some advantages. A shorter median hospital stay was observed, which may be attributed to reduced surgical trauma facilitated by the enhanced precision of ICG-guided dissection. These findings are consistent with studies suggesting that fluorescence guidance minimizes unnecessary tissue damage and optimizes the efficiency of lymph node clearance \u003csup\u003e[\u003cspan additionalcitationids=\"CR25\" citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e]\u003c/sup\u003e. However, operative time and estimated blood loss were similar between the groups, suggesting that the procedural complexity and overall surgical risks remain largely unaffected. Importantly, complication rates, including intraoperative bleeding, anastomotic leakage, and infections, were low and comparable between the groups, supporting the safety and feasibility of ICG-guided procedures in clinical practice.\u003c/p\u003e \u003cp\u003eKaplan-Meier survival analyses revealed no significant differences between the ICG-LND and control groups in OS, RFS, or LR rates during follow-up period. Both groups demonstrated high survival rates at the 3-year mark, with comparable outcomes. The Cox regression analyses further supported these findings, as ICG-LND showed no significant impact on OS or RFS. These results suggest that while ICG enhances surgical precision, it does not confer significant advantages in oncological outcomes. The low rates of local and distant recurrence observed across the cohort emphasize the importance of meticulous surgical technique in achieving successful outcomes. These findings are consistent with reports from high-volume centers, which indicate that standardized lateral lymph node dissection (LLND) protocols can provide excellent locoregional control, regardless of adjunctive measures such as ICG. \u003csup\u003e[\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e, \u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e]\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eThe versatility of ICG extends beyond LLND, with established applications in colorectal cancer surgery, such as assessing bowel perfusion during anastomosis, identifying sentinel lymph nodes, and mapping lymphatic drainage. These applications have demonstrated significant potential in reducing surgical complications and improving perioperative outcomes \u003csup\u003e[\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e, \u003cspan additionalcitationids=\"CR29\" citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e]\u003c/sup\u003e. However, in the specific context of LLND, the findings of this study indicate that the impact of ICG on long-term oncological outcomes is modest. This aligns with studies reporting that while ICG improves intraoperative visualization, its direct influence on survival or recurrence rates may be limited. Nevertheless, the reduction in surgical variability and the potential for facilitating learning curves in less experienced surgeons highlight its value as an adjunctive tool.\u003c/p\u003e \u003cp\u003eThe adoption of ICG in colorectal cancer surgery varies widely across regions. In Japan and other Asian countries where LLND is routinely performed, studies have reported that ICG enhances lymph node clearance and may improve outcomes in specific patient subgroups \u003csup\u003e[\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e, \u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e]\u003c/sup\u003e. In contrast, Western countries, where LLND is less commonly practiced, remain skeptical about the cost-effectiveness of ICG, particularly in the absence of robust evidence linking its use to improved survival outcomes. This regional disparity underscores the need for standardized protocols and further research to clarify the role of ICG in diverse clinical settings.\u003c/p\u003e \u003cp\u003eSeveral challenges limit the broader adoption of ICG-guided LLND. Although a sample size calculation was conducted in this study, the high survival rates observed within the study population raise concerns about potential underpowering. Given the possibility of small, yet clinically significant differences being overlooked, the study may have lacked sufficient statistical power to detect subtle treatment effects. This limitation could affect the accuracy and generalizability of the findings. To address this issue, future studies should consider increasing the sample size or employing alternative methodologies to ensure robust statistical power, thereby enabling a more comprehensive and reliable assessment of treatment outcomes.. Moreover, the retrospective nature of this study, introduces inherent biases that could influence the findings. A longer follow-up period may be necessary to capture late recurrences or survival differences, emphasizing the importance of prospective, multicenter trials. At last, this male-dominated population in this study, with narrower pelvic anatomies, may complicate pelvic dissection, especially for mid- to low-rectal tumors. The use of rigid laparoscopic instruments in confined spaces could impact operating time and specimen quality. While robotic systems, such as the Da Vinci system with FireFly mode, can address many of these challenges\u003csup\u003e[\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e, \u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e]\u003c/sup\u003e, further research is needed to compare laparoscopic and robotic LLND in rectal cancer patients to better assess the advantages of robotic surgery.\u003c/p\u003e \u003cp\u003eDespite these challenges, ICG\u0026rsquo;s integration with emerging technologies such as artificial intelligence and molecular imaging represents an exciting avenue for future research. Artificial intelligence could enhance the detection of micro-metastases and refine surgical strategies by integrating fluorescence imaging data with preoperative imaging and clinical parameters \u003csup\u003e[\u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e, \u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e]\u003c/sup\u003e. Cost-effectiveness analyses will also be critical, particularly in resource-limited settings where the widespread adoption of ICG remains challenging. Additionally, standardizing the protocols for ICG injection and fluorescence imaging could further optimize its utility in clinical practice.\u003c/p\u003e \u003cp\u003eIn conclusion, this study provides valuable evidence on the use of ICG-guided LLND in mid-to-lower rectal cancer. While ICG improves intraoperative visualization and facilitates lymph node dissection, its impact on long-term oncological outcomes, including survival and recurrence rates, appears limited. These findings emphasize the need for rigorous prospective trials to validate the prognostic value of ICG in colorectal cancer surgery. Until such evidence emerges, ICG should be regarded as a complementary tool for enhancing surgical precision rather than a transformative technique for improving survival outcomes.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe research protocol received approval from the Ethics Advisory Committee of the Chinese Academy of Medical Sciences Cancer Hospital, as well as from the institutional review boards of each participating center. \u0026nbsp; Given the retrospective design of the study, written informed consent was not required, and an opt-out method was employed to disclose study details. This research was in compliance with the Helsinki Declaration.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll authors have approved the final version of the article and agree the submission. This article didn\u0026rsquo;t present images or other personal or clinical details of participants.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe datasets used and/or analysed during the current study are available from the corresponding author on reasonable request.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting Interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare no conflict of interest.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis research was funded by the National Key Research and Development Program (No. 2022YFC2505003), CAMS Innovation Fund for Medical Sciences (No. 2022-12M-C\u0026T-B-057).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors\u0026apos; contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWenlong Qiu: Conceptualization, Methodology, Formal analysis, investigation, Writing - original draft.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eYu Liu: Resources, Data curation, Writing - review \u0026amp; editing.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eShiwen Mei: Resources, Data curation, Writing - review \u0026amp; editing.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eYuegang Li: Resources, Data curation, Writing - review \u0026amp; editing.\u003c/p\u003e\n\u003cp\u003eJichuan Quan: Resources, Data curation, Writing - review \u0026amp; editing.\u003c/p\u003e\n\u003cp\u003eQian Liu: Conceptualization, Methodology, Writing - review \u0026amp; editing, Supervision, Project administration.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgments\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors would like to thank the patients who participated in this study.\u0026nbsp;\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e \u003cli\u003e\u003cspan\u003eChoi GS, Kim HJ. 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Surg Endosc, 34(1): 469\u0026ndash;76.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eZhou S-C, Tian Y-T, Wang X-W, Zhao C-D, Ma S, Jiang J et al. Application of indocyanine green-enhanced near-infrared fluorescence-g uided imaging in laparoscopic lateral pelvic lymph node dissection for middle-low rectal cancer. World J Gastroenterol, 25(31): 4502\u0026ndash;11.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKawada K, Yoshitomi M, Inamoto S, Sakai Y. Indocyanine Green Fluorescence-Guided Laparoscopic Lateral Lymph Node Dissection for Rectal Cancer. Dis Colon Rectum, 62(11): 1401.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eWatanabe J, Ohya H, Sakai J, Suwa Y, Goto K, Nakagawa K et al. Long-term outcomes of indocyanine green fluorescence imaging-guided la paroscopic lateral pelvic lymph node dissection for clinical stage II/ III middle-lower rectal cancer: a propensity score-matched cohort stud y. Tech Coloproctol, 27(9): 759\u0026ndash;67.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSoran A, Senol K, Lupinacci K. Navigating Lymphedema: The Impact of Indocyanine Green Lymphography on Personalized Therapy Outcomes in Breast Cancer Patients. Clin Breast Cancer: S1526-8209(1524)00288-X.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eShevchenko I, Serban D, Dascalu AM, Tribus L, Alius C, Cristea BM et al. Factors Affecting the Efficiency of Near-Infrared Indocyanine Green (N IR/ICG) in Lymphatic Mapping for Colorectal Cancer: A Systematic Revie w. Cureus, 16(2): e55290.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSon GM, Yun MS, Lee IY, Im SB, Kim KH, Park SB et al. Clinical Effectiveness of Fluorescence Lymph Node Mapping Using ICG fo r Laparoscopic Right Hemicolectomy: A Prospective Case-Control Study. Cancers (Basel), 15(20): 4927.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSueda T, Yasui M, Nishimura J, Kagawa Y, Kitakaze M, Mori R et al. Prognostic impact of lateral sentinel lymph node biopsy using indocyan ine green on oncological outcomes for clinical stage II/III lower rect al cancer without suspected lateral lymph node metastasis. Langenbecks Arch Surg, 409(1): 311.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKehagias D, Lampropoulos C, Bellou A, Kehagias I. The use of indocyanine green for lateral lymph node dissection in rect al cancer-preliminary data from an emerging procedure: a systematic re view of the literature. Tech Coloproctol, 28(1): 53.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLim MGL, Lopez MPJ, Onglao MAS, Monroy HJ 3rd, Sacdalan MDP. Indocyanine Green (ICG) Fluorescence in the Assessment of Vascularity of Anastomotic Margins in Colorectal Surgery in a Lower Middle-Income Country (LMIC) Hospital. Acta Med Philipp, 58(16): 8\u0026ndash;13.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSun Y, Tang Z, Xu Z, Chen Z, Huang S, Wang X et al. Indocyanine green near-infrared fluorescence-assisted video endoscopic inguinal lymph node dissection for rectal cancer: a single-center exp erience. Tech Coloproctol, 28(1): 64.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eDai J-Y, Han Z-J, Wang J-D, Liu B-S, Liu J-Y, Wang Y-C. Short-term outcomes of near-infrared imaging using indocyanine green i n laparoscopic lateral pelvic lymph node dissection for middle-lower r ectal cancer: A propensity score-matched cohort analysis. Front Med (Lausanne), 9: 1039928.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGuo H, Luo Y, Fu Z, Wang D. Indocyanine green fluorescence imaging for lymph node detection and lo ng-term clinical outcomes in colorectal cancer surgery: A systematic r eview and meta-analysis. World J Surg: \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1002/wjs.12412\u003c/span\u003e\u003cspan address=\"10.1002/wjs.12412\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eCassinotti E, Costa S, De Pascale S, Oreggia B, Palazzini G, Boni L. How to reduce surgical complications in rectal cancer surgery using fl uorescence techniques. Minerva Chir, 73(2): 210\u0026ndash;6.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGr\u0026ouml;ne J, Koch D, Kreis ME. Impact of intraoperative microperfusion assessment with Pinpoint Perfu sion Imaging on surgical management of laparoscopic low rectal and ano rectal anastomoses. Colorectal Dis, 17 Suppl 3: 22\u0026ndash;8.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eJafari MD, Lee KH, Halabi WJ, Mills SD, Carmichael JC, Stamos MJ et al. 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Surg Technol Int, 38: 160\u0026ndash;6.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLim ZY, Mohan S, Balasubramaniam S, Ahmed S, Siew CCH, Shelat VG. Indocyanine green dye and its application in gastrointestinal surgery: The future is bright green. World J Gastrointest Surg, 15(9): 1841\u0026ndash;57.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMa Z, Wang F, Wang W, Zhong Y, Dai H. Deep learning for in vivo near-infrared imaging. Proc Natl Acad Sci U S A, 118(1): e2021446118.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"bmc-surgery","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bsur","sideBox":"Learn more about [BMC Surgery](http://bmcsurg.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bsur/default.aspx","title":"BMC Surgery","twitterHandle":"@BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Indocyanine green, Lateral lymph node dissection, Rectal cancer, Fluorescence-guided surgery, Oncological outcomes","lastPublishedDoi":"10.21203/rs.3.rs-5570995/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-5570995/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e \u003cp\u003eLateral lymph node dissection (LLND) is a key component of surgical treatment for locally advanced mid-to-lower rectal cancer. While indocyanine green (ICG) fluorescence guidance has been proposed to enhance surgical precision, its impact on long-term oncological outcomes remains unclear.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eThis retrospective, multicenter study compared ICG-assisted laparoscopic LLND (ICG-LND) with conventional laparoscopic LLND in patients with mid-to-lower rectal cancer between January 2018 and June 2022. Outcomes included 3-year overall survival (OS), recurrence-free survival (RFS), local recurrence rates, and distant metastasis rates. Kaplan-Meier analysis and Cox proportional hazards regression models were used to evaluate survival outcomes.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eThe study included 258 patients (ICG-LND: 79; control: 179). The ICG-LND group had a slightly higher median number of harvested lateral lymph nodes (9 [IQR: 5\u0026ndash;13] vs. 7 [IQR: 4\u0026ndash;13]), but the difference was not significant (P\u0026thinsp;=\u0026thinsp;0.611). Similarly, positive lateral lymph node counts showed no significant difference (P\u0026thinsp;=\u0026thinsp;0.455). Median postoperative hospital stays were shorter in the ICG-LND group (6 [IQR: 5\u0026ndash;8] vs. 7 [IQR: 6\u0026ndash;9] days, P\u0026thinsp;\u0026lt;\u0026thinsp;0.001). Survival analysis showed no significant differences between groups in OS (5-year: 84.6% vs. 86.1%, P\u0026thinsp;=\u0026thinsp;0.884), RFS, or recurrence rates (local: 6.3% vs. 6.7%; distant: 10.1% vs. 10.8%).\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e \u003cp\u003eICG-LND shortens postoperative recovery but does not enhance long-term oncological outcomes, including survival and recurrence rates. Further prospective studies are needed to validate its prognostic value.\u003c/p\u003e","manuscriptTitle":"The Short and Long Oncological Outcome of Indocyanine Green for Lateral Lymph Node Dissection in Mid-low Rectum Cancer","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-04-15 01:20:42","doi":"10.21203/rs.3.rs-5570995/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2025-04-22T16:53:14+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-04-22T16:53:01+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-04-21T05:51:47+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-04-12T07:44:30+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"134877650538825937496101247451646295539","date":"2025-04-12T00:34:10+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"84431727435036339438134164398592015793","date":"2025-04-11T15:10:46+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-04-11T14:54:05+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-04-11T07:38:39+00:00","index":"","fulltext":""},{"type":"submitted","content":"BMC Surgery","date":"2025-03-31T14:51:09+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-surgery","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bsur","sideBox":"Learn more about [BMC Surgery](http://bmcsurg.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bsur/default.aspx","title":"BMC Surgery","twitterHandle":"@BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"57c3ee07-3349-4796-b23d-4aaf624821bc","owner":[],"postedDate":"April 15th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2025-06-30T15:38:34+00:00","versionOfRecord":[],"versionCreatedAt":"2025-04-15 01:20:42","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-5570995","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-5570995","identity":"rs-5570995","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}