This study aims to develop a prediction model for lymph node metastasis (LNM) in colorectal cancer (CRC) patients using common clinicopathologic data and a nomogram. The model seeks to uncover correlations between LNM and clinical indicators, providing an effective tool to identify high-risk patients, aiding clinical decision-making, and enhancing patient prognosis.

We conducted a retrospective analysis of CRC patients diagnosed between January 2021 and December 2023 at Zhuzhou Hospital Affiliated to Xiangya School of Medicine, Central South University. Risk predictors for LNM were identified through comparative analysis and Least Absolute Shrinkage and Selection Operator (LASSO) logistic regression. Nomograms were then utilized to predict the probability of metastasis, and their performance was assessed using calibration curves, receiver operating characteristic (ROC) curves, and decision curve analysis.

The study comprised 869 CRC patients, with 435 cases allocated to the training set and 434 cases to the validation set. First, 12 potential risk factors for LNM in CRC patients were identified through comparative analysis in the training set. Next, nine independent predictors (T stage, vascular tumor thrombus, PMS2, MSH2, KRAS, BRAF, PIK3CA, leukocyte, and neutrophil) of LNM occurrence were refined using LASSO regression and multivariate logistic regression models. Subsequently, a clinical nomogram was developed based on these independent predictors of LNM. The nomogram exhibited a C-index of 0.751 (95% CI [0.728-0.774]), indicating its robust predictive value, which was further validated in the independent validation set.

T stage, vascular tumor thrombus, PMS2, MSH2, KRAS, BRAF, and neutrophil emerged as significant risk factors for LNM in CRC, while leukocytes appeared to be protective. These findings emphasize the importance of comprehensive risk assessment and personalized therapeutic strategies in CRC management.

Background: Colon cancer is known as one of the most prevalent malignancies in the world. This well-known pathology requires accurate lymph node dissection to achieve effective staging and improved treatment outcomes. Indocyanine green fluorescence imaging has been used as a new technique for enhancing lymph node visualization during surgical intervention. The high rates of local recurrence in colon cancer patients require innovative methods to improve lymphatic mapping and lymph node dissection. This review evaluates the clinical utility and efficacy of ICG imaging in enhancing lymph node accuracy in colon cancer surgery. Materials and methods: A systematic search was conducted in October 2024 (last day of consulting the database was 16 November) across Web of Science, Scopus, and PubMed to identify studies published from 2020 onwards focusing on the use of indocyanine green in colon cancer surgeries. The search terms used were "indocyanine green", "ICG", "fluorescent imaging", "near-infrared imaging", "colon cancer", "colorectal cancer", "colon carcinoma"," colon neoplasms", "surgery", "surgical procedure", "surgical resection", surgical precision". The search followed PRISMA guidelines. The records underwent a two-phase independent screening process conducted by the authors, first based on the title and abstract, followed by full record evaluation. Articles were excluded following certain exclusion criteria: non-human studies; restricted access publications; other publication type than article (review, meta-analysis, questionnaire-based study, case report, etc.), studies focusing on other diseases or studies that focused on the surgical treatment of metastasis from colon cancer; foreign language (non-English); no data of interest for the current review; studies that focused on rectal cancer and that grouped rectal and colon cancer. Data extraction involved both quantitative and qualitative data, such as detection rates, sensitivity, specificity, and other surgical outcomes. Risk of bias was assessed using ROBINS-I, J Joanna Briggs Institute (JBI) Critical Appraisal Checklist, and the Newcastle-Ottawa Scale, depending on study type. The study was not preregistered in PROSPERO. However, to ensure methodological rigor and transparency, it was retrospectively registered in Open Science Framework (OSF). Results: From the 3300 records initially identified, 9 studies were included in this review. Detection rates varied from 55% to 100%, with the highest rate reported in robot-assisted surgeries. The studies showed an improved lymph node detection and lymphatic flow accuracy using ICG fluorescence. Discussion: ICG fluorescence demonstrated substantial benefits, improving staging accuracy and potentially reducing recurrence rates by guiding the lymphadenectomy. The variability observed in detection rates is largely attributed to differences in ICG administration, cancer stage, and surgical approaches. Conclusions: ICG-guided surgery for colon cancer represents a promising advancement, enhancing lymph node detection and staging accuracy. Large-scale randomized trials are essential to establish standardized protocols and validate the efficacy in improving surgical outcomes.

Patients with cT1-2 colon cancer (CC) have a 10-20% risk of lymph node metastases. Sentinel lymph node identification (SLNi) could improve staging and reduce morbidity in future organ-preserving CC surgery. This pilot study aimed to assess safety and feasibility of robot-assisted fluorescence-guided SLNi using submucosally injected indocyanine green (ICG) in patients with cT1-2N0M0 CC.

Ten consecutive patients with cT1-2N0M0 CC were included in this prospective feasibility study. Intraoperative submucosal, peritumoral injection of ICG was performed during a colonoscopy. Subsequently, the near-infrared fluorescence 'Firefly' mode of the da Vinci Xi robotic surgical system was used for SLNi. SLNs were marked with a suture, after which a segmental colectomy was performed. The SLN was postoperatively ultrastaged using serial slicing and immunohistochemistry, in addition to the standard pathological examination of the specimen. Colonoscopy time, detection time (time from ICG injection to first SLNi), and total SLNi time were measured (time from the start of colonoscopy to start of segmental resection). Intraoperative, postoperative, and pathological outcomes were registered.

In all patients, at least one SLN was identified (mean 2.3 SLNs, SLN diameter range 1-13 mm). No tracer-related adverse events were noted. Median colonoscopy time was 12 min, detection time was 6 min, and total SLNi time was 30.5 min. Two patients had lymph node metastases present in the SLN, and there were no patients with false negative SLNs. No patient was upstaged due to ultrastaging of the SLN after an initial negative standard pathological examination. Half of the patients unexpectedly had pT3 tumours.

Robot-assisted fluorescence-guided SLNi using submucosally injected ICG in ten patients with cT1-2N0M0 CC was safe and feasible. SLNi was performed in an acceptable timespan and SLNs down to 1 mm were detected. All lymph node metastases would have been detected if SLN biopsy had been performed.

The distinction between D3 lymph nodes and actual lymphatic pathways in primary tumors can be difficult during surgery, making it challenging to confirm the completeness of D3 lymph node dissection. Fluorescence lymph node mapping (FLNM) is a promising method for lymph node visualization.

This study aimed to assess whether FLNM enhances the effectiveness of D3 lymph node dissection in patients with right-sided colon cancer.

Endoscopic submucosal indocyanine green injection were performed on the distal margin of the colon cancer. In an FLNM group, the lymphatic drainage pathway and distribution of D3 lymph nodes were explored. Pathological evaluations were conducted for the fluorescent D3 and non-fluorescent D3 lymph nodes.

The FLNM group showed a significantly higher number of harvested lymph nodes in the D3 area. In stage III patients, the proportion of D3 lymph node metastasis was significantly higher in the FLNM group. The harvested D3 lymph node count showed a proportional correlation with a metastatic lymph node count of up to 15.

FLNM could be considered a promising new strategy to potentially increase harvested D3 lymph node counts in colon cancer surgery.

Indocyanine green (ICG) is a water-soluble fluorescent dye that is minimally toxic and widely used in gastrointestinal surgery. ICG facilitates anatomical identification of structures (e.g., ureters), assessment of lymph nodes, biliary mapping, organ perfusion and anastomosis assessment, and aids in determining the adequacy of oncological margins. In addition, ICG can be conjugated to artificially created antibodies for tumour markers, such as carcinoembryonic antigen for colorectal, breast, lung, and gastric cancer, prostate-specific antigen for prostate cancer, and cancer antigen 125 for ovarian cancer. Although ICG has shown promising results, the optimization of patient factors, dye factors, equipment, and the method of assessing fluorescence intensity could further enhance its utility. This review summarizes the clinical application of ICG in gastrointestinal surgery and discusses the emergence of novel dyes such as ZW-800 and VM678 that have demonstrated appropriate pharmacokinetic properties and improved target-to-background ratios in animal studies. With the emergence of robotic technology and the increasing reporting of ICG utility, a comprehensive review of clinical application of ICG in gastrointestinal surgery is timely and this review serves that aim.

An optimized lymph node yield leads to better survival in colon cancer, but extended lymphadenectomy is not associated with survival benefits. Lymphatic mapping shows several colon cancers feature aberrant drainage pathways inducing local recurrence when not resected. Currently, different protocols exist for lymphatic mapping procedures. This meta-analysis assessed which protocol has the best capacity to detect tumor-draining and possibly metastatic lymph nodes. A systematic review was conducted according to PRISMA guidelines, including prospective trials with in vivo tracer application. The risk of bias was evaluated using the QUADAS-2 tool. Traced lymph nodes, total resected lymph nodes, and aberrant drainage detection rate were analyzed. Fifty-eight studies met the inclusion criteria, of which 42 searched for aberrant drainage. While a preoperative tracer injection significantly increased the traced lymph node rates compared to intraoperative tracing (30.1% (15.4, 47.3) vs. 14.1% (11.9, 16.5), p = 0.03), no effect was shown for the tracer used (p = 0.740) or the application sites comparing submucosal and subserosal injection (22.9% (14.1, 33.1) vs. 14.3% (12.1, 16.8), p = 0.07). Preoperative tracer injection resulted in a significantly higher rate of detected aberrant lymph nodes compared to intraoperative injection (26.3% [95% CI 11.5, 44.0] vs. 2.5% [95% CI 0.8, 4.7], p < 0.001). Analyzing 112 individual patient datasets from eight studies revealed a significant impact on aberrant drainage detection for injection timing, favoring preoperative over intraoperative injection (OR 0.050 [95% CI 0.010-0.176], p < 0.001) while indocyanine green presented itself as the superior tracer (OR 0.127 [95% CI 0.018-0.528], p = 0.012). Optimized lymphatic mapping techniques result in significantly higher detection of aberrant lymphatic drainage patterns and thus enable a personalized approach to reducing local recurrence.

In recent years, the use of Indocyanine Green (ICG) fluorescence-guided surgery during open and laparoscopic procedures has exponentially expanded across various clinical settings. The European Association of Endoscopic Surgery (EAES) initiated a consensus development conference on this topic with the aim of creating evidence-based statements and recommendations for the surgical community.

An expert panel of surgeons has been selected and invited to participate to this project. Systematic reviews of the PubMed, Embase and Cochrane libraries were performed to identify evidence on potential benefits of ICG fluorescence-guided surgery on clinical practice and patient outcomes. Statements and recommendations were prepared and unanimously agreed by the panel; they were then submitted to all EAES members through a two-rounds online survey and results presented at the EAES annual congress, Barcelona, November 2021.

A total of 18,273 abstracts were screened with 117 articles included. 22 statements and 16 recommendations were generated and approved. In some areas, such as the use of ICG fluorescence-guided surgery during laparoscopic cholecystectomy, the perfusion assessment in colorectal surgery and the search for the sentinel lymph nodes in gynaecological malignancies, the large number of evidences in literature has allowed us to strongly recommend the use of ICG for a better anatomical definition and a reduction in post-operative complications.

Overall, from the systematic literature review performed by the experts panel and the survey extended to all EAES members, ICG fluorescence-guided surgery could be considered a safe and effective technology. Future robust clinical research is required to specifically validate multiple organ-specific applications and the potential benefits of this technique on clinical outcomes.

Indocyanine green (ICG) is a nontoxic, albumin-bound, liver-metabolized fluorescent iodide dye that has been widely utilized in clinical applications since the mid-1950s. However, after the 1970s, in-depth research on the fluorescence properties of ICG greatly expanded its application in the medical field.

In our mini-review, we searched the relevant literature on common oncology surgeries from PubMed, including lung cancer, breast cancer, gastric cancer, colorectal cancer, liver cancer, and pituitary tumors, using keywords such as indocyanine green, fluorescence imaging technology, and near-infrared fluorescence imaging. In addition, the application of targeted ICG photothermal technology in tumor therapy is briefly mentioned.

In this mini-review, we analyzed studies on ICG fluorescence imaging in common surgical oncology and offered a thorough analysis of each form of cancer or tumor.

ICG has demonstrated significant potential in the detection and treatment of tumors in current clinical practice, although many applications are still in the preliminary stages, and multicenter studies are still required to more precisely define its indications, effectiveness, and safety.

To elucidate whether a high level of microsatellite instability (MSI-high) in colon cancer influences the CT assessment of regional lymph node (rLN) morphology and diagnostic performance on predicting pathological node-negative (pN0) patients.

We retrospectively reviewed 507 patients with cecal/proximal ascending colon cancer (age, 63.0 ± 11.6 years; MSI-stable, n = 398; MSI-high, n = 109) who underwent right hemicolectomy between July 1, 2009, and December 31, 2018. Preoperative CT images were assessed for number of rLNs, long/short diameter of the largest rLN, and CT LN grade (CTN0, low probability of metastasis; CTN1, borderline; CTN2, high probability). Sensitivity, specificity, positive predictive value and negative predictive value for predicting pN0 was calculated. Multivariable logistic regression analysis was performed. Statistical significance was defined as P < 0.05.

A study population of 507 patients (mean age ± standard deviation, 63.0 ± 11.6; 264 women) were evaluated. In patients with rLN metastasis, the rLN long axis (pN1: P = 0.013, pN2: P = 0.039) and short axis (pN1: P = 0.001, pN2: P = 0.009) were both longer in MSI-high tumors compared with MSI-stable tumors. High specificity for predicting pN0 was only achieved in MSI-high tumors [sensitivity_MSI-stable = 58.3% (n = 137/235), specificity_MSI-stable = 71.2% (n = 116/163); sensitivity_MSI-high = 38.4% (n = 33/86), specificity_MSI-high = 91.3% (n = 21/23)]. Multivariable logistic regression indicated MSI-high (P < 0.001, odds ratio = 3.701), smaller LN long axis (P = 0.023, odds ratio = 0.905), and lower CT LN grade (CTN0: P = 0.009, odds ratio = 2.987; CTN1: P = 0.014, odds ratio = 2.195) as significant parameters in predicting pN0.

MSI-high colon cancer is associated with larger rLNs and high specificity for predicting pN0 on CT assessment.

Fluorescence imaging in colorectal surgery is considered a novel predominantly intraoperative method of ensuring a greater surgical success. The use of fluorescence is linked to advanced tumor visualization and projection of its lymphatics, both vessels and nodes, which results in a higher chance of achieving a total excision. Additionally, iatrogenic complications prove to be reduced using fluorescence during the surgical excision. The combination of fluorescence and artificial intelligence to better facilitate oncological surgery will soon become an established approach in operating rooms worldwide.

The identification of sentinel lymph nodes is a valuable oncological method, which aims at mapping lymphatic drainage and has the advantage of correctly staging the disease and assessing prognosis. Lymph node invasion is an important prognostic feature. In colorectal cancer, lymphadenectomy is not influenced by the positive or negative status of the sentinel lymph node. The identification of lymph nodes with possible invasion by staining the primary tumor with methylene blue can lead to improved staging and management. In other words, the consequent administration of neoadjuvant therapy (chemotherapy) to the appropriate patients may result in lower recurrence rates. Thus, the aim of the present study was to use methylene blue to identify the sentinel node/nodes in colorectal cancer and to determine whether the dye-capturing nodes were invaded by the tumor. This is a non-randomized prospective study, in which 26 patients with colon cancer with surgical indication were enrolled. Two types of methods were utilized: in vivo (16 patients) and ex vivo (10 patients). The identification rate was 75% for the in vivo technique and 60% for the ex vivo technique, resulting in a 69.26% overall identification rate. Of 18 patients with sentinel lymph nodes identified using dye, routine histological examination detected metastases in 6 (33.33%) of these patients. In conclusion, further research should be conducted into how the clinical application of sentinel node detection can be employed in colorectal cancer.

The use of fluorescence might improve the performance of the sentinel lymph node procedure in patients with colon cancer. This systematic review was conducted to gain insight in the performance and applicability of the sentinel lymph node procedure using fluorescence.

A systematic literature search was performed. Databases were searched for prospective studies concerning sentinel node identification using fluorescence in colon cancer. Detection rate, accuracy rate and sensitivity of the sentinel lymph node procedure were calculated for early stage (T1-T2) and more invasive (T3-T4) tumours.

Analyses of five included studies showed for respectively T3-T4 and T1-T2 tumours a detection rate of 90 % and 91 %, an accuracy rate of 77 % and 98 %, and a sensitivity of 30 % and 80 %.

The sentinel lymph node procedure using fluorescence in early stage (T1-T2) colon cancer seems to be promising. Larger cohorts are necessary to confirm these results.

Nowadays, surgical innovations incorporate new technological conquests and must be validated by evidence-based medicine. The use of augmented reality-assisted indocyanine green (ICG) fluorescence has generated a myriad of intraoperative applications such as demonstration of key anatomical landmarks, sentinel lymph nodes, and real-time assessment of local blood flow. This paper presents a systematic review of the clinical evidence regarding the applications of ICG near-infrared (NIR) fluorescence in colorectal surgery. After we removed duplicate publications and screened for eligibility, a total of 36 articles were evaluated: 23 on perfusion assessment, 10 on lymph node mapping, and 3 on intraoperative identification of ureters. Lack of homogenous studies, low statistical power, and confounding evidence were found to be common amongst publications supporting the use of ICG in colorectal surgery, raising concerns over this seductive technique's cost efficiency and redundancy. The compiled data showed that ICG NIR fluorescence may be a game-changer in particular situations, as proven for low colorectal anastomosis or lateral pelvic lymph node dissection, but it remains controversial for routine use and sentinel lymph node assessment. Further randomized studies are needed to confirm these conclusions. Future research directions include tumor-targeted fluorescence imaging and digital software for quantitative evaluation of fluorescence.