A model based on endorectal ultrasonography predicts lateral lymph node metastasis in low and middle rectal cancer

Abstract Purpose To investigate the risk factors for lymph node (LN) metastasis in low and middle rectal tumors, construct a predictive model and test the model's diagnostic efficacy. Methods The clinical and pathological data of 172 patients with rectal cancer confirmed by surgery were retrospectively evaluated, among whom 61 patients were finally included in this study. Patients were divided into positive groups and negative groups based on LN metastasis, and risk factors that might affect LN metastasis were analyzed. Finally, a risk predictive model was constructed based on the weights of each risk factor. Results Compared with pathology, the efficacy of diagnosing LN metastasis only according to conventional endorectal ultrasonography (ERUS) features of LN was not high, with sensitivity 67%, specificity 86%, positive predictive value 76%, negative predictive value 80%, and accuracy 79%. Univariate analysis showed that circumferential angle of the tumor, ultrasonic T‐ stage (UT stage), conventional ultrasound features diagnosis of LN metastasis, strain ratio (SR) of tumor were risk factors for LN metastasis, while vascular resistance index of rectal tumor was protective factor. Multivariate analysis showed that UT stage (OR = 7.188, p = 0.049), conventional ultrasound features diagnosis of LN metastasis (OR = 8.010, p = 0.025) and SR (OR = 5.022, p = 0.031) were independent risk factors for LN metastasis. These risk factors were included in logistic regression analysis and the model was established, Y = −7.3 + 1.9 X10 + 2.1 X11 + 1.6 X13 (Y = Logit[P], P: LN metastasis rate, X10: UT stage, X11: conventional ultrasound features diagnosis of LN metastasis, X13: SR). The receiver operating characteristic (ROC) curve was used to test the model's predictive efficacy, the area under the curve was 0.95, sensitivity: 95%, specificity: 87%. Hosmer–Lemeshow goodness of fit test showed X2 = 6.015, p = 0.65 (p > 0.05), indicating that the model had a high predictive value. Conclusion Evaluation of perirectal LN metastasis only based on conventional ERUS features of LN was not effective enough. UT stage of tumor, conventional ultrasound features diagnosis of LN metastasis and SR were independent risk factors for LN metastasis. The predictive model had good assessment efficacy and had certain clinical application value.


| INTRODUCTION
Currently, rectal carcinoma is one of the common gastrointestinal tumors and the incidence is increasing. 1,2 Lymph node (LN) metastasis is the main way of rectal cancer metastasis. Mesenteric LN is the most frequently involved tissue of rectal cancer diffusion and metastasis. 3 For benign tumors and early rectal cancer without LN metastasis, local resections such as endoscopic dissection and transanal endoscopic minimally invasive surgery can be selected to achieve a radical cure. 4 Such treatments reduce the damage to the patient and economic burden and improve the quality of life. If perirectal LNs metastasize, the draining regional LNs are likely to have metastasized, which is an indication of neoadjuvant chemoradiotherapy. 5 If minimally invasive surgery is selected blindly, treatment will be delayed. Therefore, accurate preoperative assessment of LN metastasis is critical to the selection of appropriate treatment, as both inadequate and excessive treatment will have a significant impact on the prognosis of patients.
Evaluation of LN metastases becomes critical in developing a treatment plan. Unfortunately, there are no clinical findings or imaging examinations that are very accurate in assessing LN metastases before surgery. Endorectal ultrasonography (ERUS) and MRI are the preferred examinations for rectal tumors. Previously, these tests were used to determine whether a LN was metastatic by morphologic characterization of the LN, however the accuracy was not high. 6,7 In addition, it cannot meet the requirements of precision medicine only by one index. 8 In this study, multiple factors related to LN metastasis were incorporated into Logistic regression to analyze the independent influencing factors of perirectal LNs metastasis. transrectal probe and a biplane probe, frequency: 5-10 MHz, the frequency could be adjusted. In addition, one-time retention enema bags and physiological saline were prepared.

| Procedure
Preparation (1) Applied the couplant to the surface of the rectal ultrasound probe and covered it with a clean condom. (2) In order to get the patient's cooperation, before the examination, the sonographers explained to the patient about the purpose of the examination to eliminate the patient's tension. (3) Two days before the examination, patients should eat less residue diet, one day before, take some liquid food, before the examination, warm water enema one to two times to remove the residue in the rectum. At the time of examination, 100-200 mL of normal saline was kept in the rectum.

Detection techniques
The patient was placed in the comfortable left decubitus position and the anus was exposed. First, the examiner performed an anal finger examination to see whether there was lumen stenosis, then the probe was slowly inserted into the anus, and the patient was

| Clinical indicators
Gender, age, carbohydrate antigen 19-9 (CA19-9), carcinoembryonic antigen (CEA), and other related data. Pathological results of LNs: the patient received surgical treatment within 2 weeks after the ultrasound examination, and the specimen was taken during the operation and sent for pathology examination quickly.

| Statistical methods
SPSS 26.0 statistical software was used for analysis. The measurement data were tested for normality first, and the T test was used for comparison between the two groups for data conforming to normal distribution, while the Mann-Whitney U test was used for nonnormally distributed data. Spearman correlation was used for correlation analysis.   Table 1 3.2 | Table 2 was the list of assignment description, and some continuous variables were converted into classified variables 3.3 | Comparison between conventional ERUS ultrasound feature evaluating lymph node metastasis and pathology Table 3 showed the comparison between pathology results and conventional ERUS ultrasound feature evaluating LN metastasis. The results showed evaluation of perirectal LN metastasis only based on conventional ERUS features was not effective enough. The correlation between separate conventional ERUS ultrasound features and LN metastasis was weak, r = 0.54, p = 0.000.  pointed out that early rectal cancer had a lower risk of LN metastasis, which were confined to the mucosa because of its shallow infiltration depth. There was almost no lymphatic supply in the rectal mucosa.

| Multivariate analyses
The intestinal lymphatic network was mainly located in the submucosa, while metastasis was more likely to occur when rectal tumors broke through the submucosa.
In addition, this study found that the stiffness of rectal tumors was also related to LN metastasis, and SR was higher in rectal tumors with LN metastasis than in tumors without LN metastasis, and the difference was statistically significant. Elastography reflects the stiffness of the lesion and has proven to be valuable in multiple organs such as the liver, breast, and prostate, [20][21][22]

CONFLICT OF INTEREST
The author has no conflict of interest to disclose.

ETHICS STATEMENT
This study was approved by the Ethics Committee of the first affili-