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This study aimed to identify independent predictive factors for the coexistence of LSTs with colorectal polyps and the independent risk factors for malignancy in LSTs with colorectal polyps. Methods This retrospective study included 229 patients diagnosed with LSTs via colonoscopy at Lianyungang First People's Hospital from January 2020 to March 2024. Patients were divided into two groups based on the presence of colorectal polyps: polyp group (n = 139) and non-polyp group (n = 90). Clinicopathological characteristics were compared between the two groups, and binary logistic regression was used to identify predictive factors for coexistence. The polyp group was further subdivided into malignant group (n = 62) and non-malignant group (n = 77) based on the degree of dysplasia. Binary logistic regression was also used to analyze the risk factors for malignant transformation of LSTs with colorectal polyps. Results Male gender (OR = 0.330, 95% CI: 0.186 - 0.586, P < 0.001) and age between 50 - 75 years (OR = 4.293, 95% CI: 1.060 - 17.376, P = 0.041) were identified as predictive factors for the coexistence of colorectal polyps with LSTs. The area under the receiver operating characteristic curve (AUC) for the predictive model was 0.703 (95% CI: 0.633 - 0.773; P < 0.001). LST diameter ≥ 2 cm (OR = 4.574, 95% CI: 1.754 - 11.933, P = 0.002), LST-G-H subtype (OR = 8.761, 95 % CI: 2.788 - 27.530, P < 0.001), and LST-G-M subtype (OR = 0.182, 95%CI: 0.039 - 0.845, P = 0.030) were identified as risk factors for malignant transformation of LSTs with colorectal polyps. The AUC for this predictive model was 0.873 (95% CI: 0.814 - 0.931, P < 0.001). Conclusion Men aged 50 - 75 with LSTs are more likely to have coexisting colorectal polyps. Larger LST diameter and mixed nodular subtype increase the risk of malignant transformation when coexisting with colorectal polyps, whereas homogeneous granular subtype may reduce this risk. Laterally spreading tumor Colorectal cancer Colorectal Polyps Malignant risk Figures Figure 1 Introduction Colorectal cancer ranks third among cancer cases worldwide and second in cancer-related deaths[ 1 ]. It originates from either polypoid or non-polypoid colorectal tumors[ 2 – 5 ]. Laterally spreading tumors (LSTs) were first described by Ohno in Japan as a type of non-polypoid tumor[ 6 ]. LSTs are defined as tumors with a maximum diameter greater than 10 mm, typically extending laterally along the colon wall rather than vertically. Morphologically, LSTs can be classified into granular type (LST-G), with a nodular surface, and non-granular type (LST-NG), with a smooth surface. LST-G can be further divided into mixed nodular type (G-M) and homogeneous type (G-H) based on the presence or absence of large irregular nodules. LST-NG can be divided into pseudo-depressed type (NG-PD) and flat elevated type (NG-FE) based on whether the surface is flat[ 5 , 7 ]. Studies have shown that LSTs account for 5.8% of early colorectal cancer cases[ 7 ]. Colorectal polyps are masses of colonic tissue that extend into the lumen from the colonic mucosa and can be categorized into neoplastic and non-neoplastic polyps (hamartomatous and inflammatory polyps[ 8 , 9 ]. In our clinical practice, we have observed that the coexistence of LSTs and colorectal polyps is common, yet relevant studies are limited. According to large-scale international case-control studies[ 10 ], the likelihood of LST patients having concomitant colorectal polyps ranges from 8.4–52.5%, despite different growth and carcinogenic pathways. Currently, three pathways are believed to lead to colorectal tumor carcinogenesis: the adenoma-carcinoma pathway, the de novo pathway, and the serrated pathway[ 11 ]. Reports indicate that most elevated polypoid lesions undergo carcinogenesis through the adenoma-carcinoma pathway, whereas superficial lesions transform malignantly via the de novo pathway[ 12 ]. Therefore, it is speculated that LSTs may transform malignantly via the de novo pathway. However, Mukawa et al.[ 13 ] found that LST-G exhibits genetic alterations similar to adenocarcinoma, suggesting that LST-G may share a similar developmental pathway with polypoid lesions leading to colorectal tumor carcinogenesis. This indicates that both colorectal polyps and LSTs have malignant potential. Thus, does the coexistence with colorectal polyps increase the malignancy of LSTs. This study aims to investigate the predictive factors and malignancy risks of LSTs coexisting with colorectal polyps by comparing the clinicopathological differences between LSTs with and without concomitant colorectal polyps. Methods This retrospective study included patients diagnosed with laterally spreading tumors (LSTs) by colonoscopy and treated at the First People's Hospital of Lianyungang from January 2020 to March 2024. Inclusion criteria were: age ≥ 18 years, endoscopically examined LSTs defined by morphology, and complete clinicopathological data. Exclusion criteria were: familial adenomatous polyposis, inflammatory bowel disease, hereditary nonpolyposis colorectal cancer, and incomplete endoscopic examination of the Ileocecal region. Out of 240 patients, 11 were excluded due to incomplete data. Patients were categorized into two groups based on the coexistence of colorectal polyps: 139 in the polyp group and 90 in the non-polyp group. Additionally, patients were divided into malignant (90) and non-malignant (139) groups based on dysplasia. The polyp group was further divided into malignant (62) and non-malignant (77) groups. The study recorded age, gender, history of colorectal polyps, diameter, location, and degree of dysplasia of LSTs and polyps. Serum tumor biomarkers: carcinoembryonic antigen (CEA), cancer antigen (CA)19 − 9, CA125 were also documented. The study adhered to the ethical guidelines of the Declaration of Helsinki and was approved by the Ethics Committee of the First People's Hospital of Lianyungang (KY-20240528001-01). Endoscopic Criteria of LSTs LSTs were classified into granular and non-granular types according to the Kudo classification. Granular types include nodular mixed and homogeneous types, while non-granular types include elevated and pseudodepressed types[ 1 ]. LST locations were categorized as ileocecal region, ascending colon, transverse colon, descending colon, sigmoid colon, and rectum. The right colon includes the cecum, ascending colon, and two-thirds of the transverse colon; the left colon includes one-third of the transverse colon, descending colon, and sigmoid colon. Histopathological Assessment The histopathological type of LST was determined according to the WHO 2010 criteria for digestive tract tumors[ 14 ]. Types include hyperplastic, low-grade, high-grade, and carcinoma. High-grade intraepithelial neoplasia and invasive carcinoma were defined as malignant, while hyperplastic and low-grade intraepithelial neoplasia were defined as non-malignant. Pathological types include proliferative polyps, serrated lesions, tubular adenomas, villous tubular adenomas, and adenocarcinoma[ 7 , 15 ]. Statistical Analysis Data were analyzed using SPSS version 24 (SPSS Inc., Chicago, IL, USA). Categorical data were analyzed using the Chi-square test or Fisher's exact test for group comparisons. Normally distributed continuous data were presented as mean ± standard deviation and assessed using the independent samples t-test. For continuous data not following a normal distribution, the Mann-Whitney U test was employed for between-group comparisons. A two-sided P-value < 0.05 indicated statistical significance. Variables with P < 0.05 were included in binary logistic regression analysis to identify predictors of LSTs with colorectal polyps and independent risk factors for malignant transformation. Results Baseline Clinicopathological Factors A total of 229 patients were included, with 90 in the non-polyp group and 139 in the polyp group (Table 1). No significant differences were found in the history of colorectal polyps ( P = 0.22), diameter ( P = 0.321), location ( P = 0.547), or morphological type ( P = 0.256) between groups. However, patients aged ≥ 50 years ( P = 0.041) and males ( P < 0.001) were more frequent in the polyp group. Tubular adenomas were the predominant pathological type of LSTs, especially in the polyp group ( P = 0.034). LSTs were more frequently located in the ascending colon(24.9%)and rectum(23.6%). Tumor markers CEA ( P = 0.069), CA199 ( P = 0.598), CA125 ( P = 0.541) were not significantly associated with colon polyps. Binary logistic regression analysis indicated that being male (OR = 0.330, 95%CI: 0.186 - 0.586, P < 0.001) and aged between 50 and 75 (OR = 4.293, 95%CI: 1.060 - 17.376, P = 0.041) were predictors of LSTs with colorectal polyps (Table 2). The AUC of the binary logistic model was 0.703 (95% CI 0.633 - 0.773; P < 0.001) (Figure 1a). Risk Factors for Malignant Lesions in LSTs Patients were divided into non-malignant (139) and malignant (90) groups based on histology. Differences were significant in location ( P < 0.001), diameter ( P < 0.001), the coexistence of colorectal polyps ( P = 0.041), and morphological type ( P < 0.001) between groups (Table 3). No significant differences were found in gender ( P = 0.206) and age ( P = 0.074). Tumor markers CEA (P = 0.848), CA125 ( P = 0.36) showed no significant differences, but CA199 was significant ( P = 0.003). Binary logistic regression analysis revealed that LSTs with a diameter > 2 cm (OR = 3.757, 95% CI: 1.774 - 7.957, P < 0.001), coexistence with colon polyps (OR = 3.884, 95% CI: 1.794 - 8.407, P < 0.001), location in the rectum (OR = 3.449, 95% CI: 1.078 - 11.030, P = 0.037), and LST-G-M (OR = 9.578, 95% CI: 3.937 - 23.301, P < 0.001), LST-NG-FE (OR = 0.201, 95% CI: 0.056 - 0.719, P = 0.014) morphological types increased the risk of malignancy (Table 4). The AUC of the binary logistic model was 0.859 (95% CI 0.812 - 0.906; P < 0.001) (Figure 1b). Risk Factors for Malignant Lesions in LSTs Coexisting with Colon Polyps In the polyp group, patients were divided into non-malignant (77) and malignant (62) groups. Significant differences were found in age ( P = 0.018), location of LST ( P = 0.006), and diameter of LST ( P < 0.001) (Table 5). No significant differences were found in gender ( P = 0.353), polyp location ( P = 0.841), polyp size ( P = 0.139), polyp number ( P = 0.377), distance between polyps and LSTs ( P = 0.804), and pathological types of polyps ( P = 0.102). In the non-malignant group, all polyps were non-malignant, while four polyps in the malignant group were malignant. However, not all histopathological types of polyps were examined and collected. No significant differences were found in CEA ( P = 0.594) and CA125 ( P = 0.362), but CA199 showed a significant difference ( P = 0.002). Binary logistic regression analysis indicated that LSTs with a diameter ≥ 2 cm (OR = 4.574, 95% CI: 1.754 - 11.933, P = 0.002), LST-G-H (OR = 8.761, 95% CI: 2.788 - 27.530, P < 0.001), and LST-G-M (OR = 0.182, 95% CI: 0.039 - 0.845, P = 0.030) were risk factors for malignant transformation in LSTs coexisting with colon polyps (Table 6). The AUC of the ROC curve was 0.873 (95% CI 0.814 - 0.931, P < 0.001) (Figure 1c). Discussion This study found that patients with LSTs are predominantly male and older, making the presence of colorectal polyps more likely. However, these two factors did not increase the malignancy risk of LSTs. Surprisingly, when further assessing the malignancy risk of LSTs coexisting with colorectal polyps, it was found that being male still did not increase the malignancy risk, but univariate analysis showed that age did increase the risk of malignancy. Previous studies [ 16 , 17 ]have indicated that LST patients are typically around 65 years old and predominantly male, similar to our study. In a retrospective study by Shen[ 18 ], the risk of coexisting colorectal polyps and LSTs increased in males and individuals aged 50 to 75, but this did not increase the malignancy risk of LSTs. Other studies [ 19 – 21 ]have pointed out that male gender and advanced age are risk factors for colorectal polyps, which explains the significant differences observed in our study when LSTs coexist with polyps, but further research is needed to determine whether advanced age increases the malignancy risk of LSTs. Next, does the diameter of LSTs increase their malignancy risk? A meta-analysis indicated that larger LSTs have a higher incidence of submucosal invasive cancer. Specifically, the incidence rates of submucosal invasive cancer for LSTs with diameters of 10–19 mm, 20–29 mm, and greater than 30 mm are 4.6%, 9.2%, and 16.5%, respectively[ 22 ]. Our study found that LSTs with a diameter greater than 2 cm are a risk factor for malignant transformation, regardless of the coexistence with colorectal polyps. This study found that tubular adenoma is the most common pathological type of LSTs. Kyeong's research also supports this view, excluding LST-NG-PD[ 23 ]. In this study, the distribution of LST subtypes was 64 cases (27.9%) of LST-G-H, 87 cases (38.0%) of LST-G-M, 57 cases (24.9%) of LST-NG-FE, and 21 cases (9.2%) of LST-NG-PD. Previous studies[ 24 ] have also reported that granular types account for 68.1% of LSTs, with LST-G-M comprising 38%; non-granular types account for 39.2%, with LST-NG-PD comprising 15.2%. Serum tumor markers are valuable adjunctive tools for the diagnosis and prognosis assessment of colorectal cancer (CRC). Liu's meta-analysis reports[ 25 ] that the sensitivity and specificity of carcinoembryonic antigen (CEA) for diagnosing CRC are 46% and 89%, respectively. In contrast, carbohydrate antigen 19 − 9 (CA199) demonstrates a lower sensitivity of approximately 30% but a higher specificity of 92%. Recent research indicates that the combined use of multiple tumor markers may enhance diagnostic and prognostic accuracy[ 26 ]. Our study observed that CA199 levels were elevated in the malignant group compared to the non-malignant group, irrespective of the presence of colonic polyps. However, due to the limited dataset, these findings should be considered preliminary, and further studies with larger sample sizes are warranted to validate these results. We further investigated the impact of LST surface morphological subtypes on malignancy risk. This study found that the malignant group had more patients with LST-G-M and LST-NG-PD, while the non-malignant group had more patients with LST-G-H and LST-NG-FE. Multiple studies [ 16 , 27 – 29 ]have found that precancerous lesions and submucosal cancer are more apparent in nodular mixed tumors within the granular type than in homogeneous tumors; in the non-granular type, pseudo-depressed tumors are more common than flat elevated tumors. Kudo's research[ 30 ] indicated that LST-NG-PD has a higher invasion rate. Our further findings suggested that when coexisting with colorectal polyps, the LST subtype LST-G-H reduces the malignancy risk, but when not considering coexistence, LST-NG-FE reduces the malignancy risk. This might be due to the small sample size, and further studies with larger samples are needed. This suggests that the endoscopic classification of LSTs is a predictor of malignancy. We also evaluated the impact of LST location on malignancy risk. Studies from Japan and Italy have shown that LSTs are mostly located in the proximal colon[ 31 ]. However, other studies [ 30 , 32 ]have pointed out that granular lesions are most commonly found in the rectum and proximal colon, whereas non-granular lesions are most commonly found in the transverse colon. In this study, 53.3% (122/229) of LSTs were located in the proximal colon, but in the malignant group, LSTs were mostly located in the distal colon, particularly the rectum. Yusuke Horiuchi's research [ 33 ]indicated that rectal LST-NG-PD tumors have a high proportion of submucosal invasive lesions, and non-granular tumors, whether LST-NG-PD or LST-NG-FE, located in the rectum may have higher malignancy than those in the colon. Other studies have reported that invasive cancer is rarely found in LST-G-H lesions[ 27 , 34 , 35 ]. This study found that in the evaluation of LST location, the rectum had the highest proportion at 40%; when coexisting with colorectal polyps, it was 36.5%; and it remained significant in multivariate analysis, while there was no significant difference in coexisting with colon polyps. This has clinical implications, suggesting that when LSTs are located in the rectum, the possibility of malignancy increases. The coexistence of colorectal polyps and LSTs is common. Previous studies[ 18 ] have pointed out that right colon polyps are the most important risk factor for predicting the malignancy of LSTs. Our study indicated that the coexistence of colorectal polyps increases the malignancy risk of LSTs, but the location and pathological morphology of colorectal polyps are not significant in the assessment, possibly due to the multiplicity of colorectal polyps, making complete statistics challenging. Conclusion When performing colonoscopy, endoscopists can assess the malignancy risk of LSTs based on the coexistence with colorectal polyps, the diameter of LSTs, the surface morphology, and the location of LSTs. However, age may increase the malignancy risk of LSTs when coexisting with colorectal polyps. For high-risk LST lesions, active endoscopic treatment should be pursued to reduce the occurrence of colorectal malignancies. This study primarily investigates the clinical characteristics and malignancy risk assessment of LSTs coexisting with colorectal polyps. Future studies can explore the clinical characteristics and malignancy risk assessment of LSTs in different locations or morphological types to further guide clinical practice. Declarations Author contributions statement Qingwen Yuan, Xuyang Liang and Jiafu Song designed the study. Zhimei Zhang, Yanqi Zhang and Shuxian Zhang collected data. Chenyan Zuo and Huahui Zhang analyzed the data and prepared the manuscript. Qingwen Yuan and Yanqi Zhang directed final version of all contents. All authors reviewed and approved the manuscript. Declaration of competing interest The authors declare no conflict of interest. Funding This work was supported by the Early Gastrointestinal Cancer Program (GTCZ-2022-JS-32-0002) Author Contribution Q.W. Y., X.Y. L. and J.F.S. designed the study. Z.M.Z., Y.Q. Z. and S. X.Z. collected data. C.Y.Z. and H.H.Z. analyzed the data and prepared the manuscript. Q.W. Y. and Y.Q.Z. directed final version of all contents. All authors reviewed and approved the manuscript. Acknowledgement The authors thank Ying Zhou for her assistance with language and the reviewers for allowing us to make improvements to the manuscript References Vlad Alexandru I, Gina G, Nicolae B, Alexandru Laurentiu C, Camelia DJM. Colorectal Cancer: From Risk Factors to Oncogenesis. Medicina (Kaunas) 2023;59(9).https://dx.doi.org/10.3390/medicina59091646 B J R, T F, A C, M F D, S Y, D M C et al. 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Endoscopy. 2001;33(8):682-6. https://dx.doi.org/10.1055/s-2001-16213 Shiro O, Shinji T, Hiroyuki K, Sayaka O, Kazuaki CJDE. Therapeutic strategy for colorectal laterally spreading tumor. Digestive Endoscopy. 2009(0):S43-6.https://dx.doi.org/10.1111/j.1443-1661.2009.00869.x Tables Tables 1-6 are available in the Supplementary Files section. Additional Declarations No competing interests reported. Supplementary Files Table1.xlsx Table2.xlsx Table3.xlsx Table4.xlsx Table5.xlsx Table6.xlsx Cite Share Download PDF Status: Posted Version 1 posted 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-4611935","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":326275750,"identity":"417822c8-c636-4954-a4ab-77c7b6535034","order_by":0,"name":"Qingwen Yuan","email":"","orcid":"","institution":"Department of Gastroenterology, the First People's Hospital of Lianyungang","correspondingAuthor":false,"prefix":"","firstName":"Qingwen","middleName":"","lastName":"Yuan","suffix":""},{"id":326275751,"identity":"10043b95-daf7-4f6d-8c5d-82fd4bd651bf","order_by":1,"name":"Zhimei Zhang","email":"","orcid":"","institution":"Department of Gastroenterology, the First People's Hospital of Lianyungang","correspondingAuthor":false,"prefix":"","firstName":"Zhimei","middleName":"","lastName":"Zhang","suffix":""},{"id":326275752,"identity":"7f584db7-835a-4753-b616-20b4eb9e6a6c","order_by":2,"name":"Yanqi Zhang","email":"","orcid":"","institution":"Department of General Practice, Tongren Hospital, Shanghai Jiao Tong University School of Medicine","correspondingAuthor":false,"prefix":"","firstName":"Yanqi","middleName":"","lastName":"Zhang","suffix":""},{"id":326275753,"identity":"435d0009-87f5-433d-8e87-9424f3e2be70","order_by":3,"name":"Shuxian Zhang","email":"","orcid":"","institution":"Department of Gastroenterology, the First People's Hospital of Lianyungang","correspondingAuthor":false,"prefix":"","firstName":"Shuxian","middleName":"","lastName":"Zhang","suffix":""},{"id":326275754,"identity":"d2cdb8cc-eaf3-46ef-92fa-dcca70fd63bb","order_by":4,"name":"Chenyan Zuo","email":"","orcid":"","institution":"Department of Gastroenterology, the First People's Hospital of Lianyungang","correspondingAuthor":false,"prefix":"","firstName":"Chenyan","middleName":"","lastName":"Zuo","suffix":""},{"id":326275755,"identity":"12359601-3cdf-4087-a2be-77d4628d767e","order_by":5,"name":"Huahui Zhang","email":"","orcid":"","institution":"Department of Gastroenterology, the First People's Hospital of Lianyungang","correspondingAuthor":false,"prefix":"","firstName":"Huahui","middleName":"","lastName":"Zhang","suffix":""},{"id":326275756,"identity":"a5109dc1-0763-4b4e-94c3-8e782b54bfdd","order_by":6,"name":"Jiafu Song","email":"","orcid":"","institution":"Department of Pulmonology, the First People's Hospital of Lianyungang","correspondingAuthor":false,"prefix":"","firstName":"Jiafu","middleName":"","lastName":"Song","suffix":""},{"id":326275757,"identity":"04105ff6-f3c4-49cd-bc0f-4f8270d9ec6e","order_by":7,"name":"Xuyang Liang","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAABBElEQVRIiWNgGAWjYBACPmYkzoEPFTY8/PwN+LWwIWlhPDjjTJqM5IwDBLQgsZkPc7YdtjFoSCCghZ352cOvbYcT+2e3XzjMcOY8jwHDAcYPH3PwOYzN3FjmzOHEGXfOFBwuqLjNY87cwCw5cxtev5hJS1QcTmy4kZNweMaZ2zyWDQfYmHnxamH/Ji1hcDhxPkgLb9s5HoMDCYS08JhJfgDasuFG+gGglgNEaSmTZjiTbrzxRg4DMJCTeSRnHGzG6xd+/uPbJH+2WcvOu5H++MOHCjt7fv7mgx8+4tECAsw8DAyODQzA4IUAxgb86kFKfjAw2DMwsD8gqHIUjIJRMApGJgAA2ORYbEWF7+IAAAAASUVORK5CYII=","orcid":"","institution":"Department of Gastroenterology, the First People's Hospital of Lianyungang","correspondingAuthor":true,"prefix":"","firstName":"Xuyang","middleName":"","lastName":"Liang","suffix":""}],"badges":[],"createdAt":"2024-06-20 12:59:57","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-4611935/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-4611935/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":60618113,"identity":"abc7c936-d1c3-4ad9-9e3b-f805d986737b","added_by":"auto","created_at":"2024-07-18 20:34:44","extension":"jpg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":40700,"visible":true,"origin":"","legend":"\u003cp\u003eReceiver operating characteristic curve of a binary logistic regression model. (a) Factors associated with the coexistence of LSTs and colorectal polyps included males aged 50 - 75years. The AUC was 0.703 (95% CI 0.633 - 0.773; \u003cem\u003eP \u003c/em\u003e\u0026lt; 0.001). (b) Factors associated with malignant LSTs in enrolled subjects included coexisting with polyps, LSTs located in the Rectum colon , LSTs<2cm and LST-G-M,LST-NG-FE. The AUC was 0.859 (95% CI 0.812 - 0.906; \u003cem\u003eP \u003c/em\u003e\u0026lt; 0.001). (c) Factors associated with malignant LSTs in the polyp group included LSTs located in the Rectum colon simultaneous , LSTs<2cm, LST-G-H, and LST-G-M. The AUC was 0.873 (95% CI 0.814 - 0.931, \u003cem\u003eP \u003c/em\u003e\u0026lt; 0.001)\u003c/p\u003e","description":"","filename":"1.jpg","url":"https://assets-eu.researchsquare.com/files/rs-4611935/v1/b6fb1ebf1835ccaa5fc4c077.jpg"},{"id":60988104,"identity":"dd1452f0-eda7-4b0b-944a-97ffe342f64e","added_by":"auto","created_at":"2024-07-24 10:34:40","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":441156,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4611935/v1/f019f424-63a5-49a2-b693-30efeecf19d7.pdf"},{"id":60618118,"identity":"bd90f6e1-1806-41f6-8f1d-c38dd4fb0053","added_by":"auto","created_at":"2024-07-18 20:34:44","extension":"xlsx","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":13160,"visible":true,"origin":"","legend":"","description":"","filename":"Table1.xlsx","url":"https://assets-eu.researchsquare.com/files/rs-4611935/v1/aaea67be5a8e46f0d90527d9.xlsx"},{"id":60620166,"identity":"5b544e64-a6ec-4b81-abbd-8e2919064855","added_by":"auto","created_at":"2024-07-18 20:50:44","extension":"xlsx","order_by":2,"title":"","display":"","copyAsset":false,"role":"supplement","size":10160,"visible":true,"origin":"","legend":"","description":"","filename":"Table2.xlsx","url":"https://assets-eu.researchsquare.com/files/rs-4611935/v1/ae6e65fa1c23d6f189c8299e.xlsx"},{"id":60618114,"identity":"ec86dbd2-2932-4217-8351-295d86b4d6ff","added_by":"auto","created_at":"2024-07-18 20:34:44","extension":"xlsx","order_by":3,"title":"","display":"","copyAsset":false,"role":"supplement","size":11991,"visible":true,"origin":"","legend":"","description":"","filename":"Table3.xlsx","url":"https://assets-eu.researchsquare.com/files/rs-4611935/v1/db15bfc59e9507a517791203.xlsx"},{"id":60618115,"identity":"f055b0d8-2e56-4ec5-abb8-f3bffe003de3","added_by":"auto","created_at":"2024-07-18 20:34:44","extension":"xlsx","order_by":4,"title":"","display":"","copyAsset":false,"role":"supplement","size":10438,"visible":true,"origin":"","legend":"","description":"","filename":"Table4.xlsx","url":"https://assets-eu.researchsquare.com/files/rs-4611935/v1/7aab3e8d481860bff8ec67f9.xlsx"},{"id":60618119,"identity":"3716afaf-3d76-4beb-9f16-a0e44cb48c31","added_by":"auto","created_at":"2024-07-18 20:34:45","extension":"xlsx","order_by":5,"title":"","display":"","copyAsset":false,"role":"supplement","size":13155,"visible":true,"origin":"","legend":"","description":"","filename":"Table5.xlsx","url":"https://assets-eu.researchsquare.com/files/rs-4611935/v1/4930a6690d47dcecc56117d8.xlsx"},{"id":60619214,"identity":"eaab5681-e82c-4fdb-a275-09a47d510d02","added_by":"auto","created_at":"2024-07-18 20:42:44","extension":"xlsx","order_by":6,"title":"","display":"","copyAsset":false,"role":"supplement","size":12288,"visible":true,"origin":"","legend":"","description":"","filename":"Table6.xlsx","url":"https://assets-eu.researchsquare.com/files/rs-4611935/v1/66f072b6dfd1a1223b509ea7.xlsx"}],"financialInterests":"No competing interests reported.","formattedTitle":"Predictive Factors for the Coexistence of Colorectal Lateral Spreading Tumors and Colorectal Polyps, and Risk Factors for Malignant Transformation","fulltext":[{"header":"Introduction","content":"\u003cp\u003eColorectal cancer ranks third among cancer cases worldwide and second in cancer-related deaths[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. It originates from either polypoid or non-polypoid colorectal tumors[\u003cspan additionalcitationids=\"CR3 CR4\" citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. Laterally spreading tumors (LSTs) were first described by Ohno in Japan as a type of non-polypoid tumor[\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. LSTs are defined as tumors with a maximum diameter greater than 10 mm, typically extending laterally along the colon wall rather than vertically. Morphologically, LSTs can be classified into granular type (LST-G), with a nodular surface, and non-granular type (LST-NG), with a smooth surface. LST-G can be further divided into mixed nodular type (G-M) and homogeneous type (G-H) based on the presence or absence of large irregular nodules. LST-NG can be divided into pseudo-depressed type (NG-PD) and flat elevated type (NG-FE) based on whether the surface is flat[\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. Studies have shown that LSTs account for 5.8% of early colorectal cancer cases[\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eColorectal polyps are masses of colonic tissue that extend into the lumen from the colonic mucosa and can be categorized into neoplastic and non-neoplastic polyps (hamartomatous and inflammatory polyps[\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e, \u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. In our clinical practice, we have observed that the coexistence of LSTs and colorectal polyps is common, yet relevant studies are limited. According to large-scale international case-control studies[\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e], the likelihood of LST patients having concomitant colorectal polyps ranges from 8.4\u0026ndash;52.5%, despite different growth and carcinogenic pathways. Currently, three pathways are believed to lead to colorectal tumor carcinogenesis: the adenoma-carcinoma pathway, the de novo pathway, and the serrated pathway[\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. Reports indicate that most elevated polypoid lesions undergo carcinogenesis through the adenoma-carcinoma pathway, whereas superficial lesions transform malignantly via the de novo pathway[\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. Therefore, it is speculated that LSTs may transform malignantly via the de novo pathway. However, Mukawa et al.[\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e] found that LST-G exhibits genetic alterations similar to adenocarcinoma, suggesting that LST-G may share a similar developmental pathway with polypoid lesions leading to colorectal tumor carcinogenesis. This indicates that both colorectal polyps and LSTs have malignant potential. Thus, does the coexistence with colorectal polyps increase the malignancy of LSTs.\u003c/p\u003e \u003cp\u003eThis study aims to investigate the predictive factors and malignancy risks of LSTs coexisting with colorectal polyps by comparing the clinicopathological differences between LSTs with and without concomitant colorectal polyps.\u003c/p\u003e"},{"header":"Methods","content":"\u003cp\u003eThis retrospective study included patients diagnosed with laterally spreading tumors (LSTs) by colonoscopy and treated at the First People's Hospital of Lianyungang from January 2020 to March 2024. Inclusion criteria were: age\u0026thinsp;\u0026ge;\u0026thinsp;18 years, endoscopically examined LSTs defined by morphology, and complete clinicopathological data. Exclusion criteria were: familial adenomatous polyposis, inflammatory bowel disease, hereditary nonpolyposis colorectal cancer, and incomplete endoscopic examination of the Ileocecal region. Out of 240 patients, 11 were excluded due to incomplete data. Patients were categorized into two groups based on the coexistence of colorectal polyps: 139 in the polyp group and 90 in the non-polyp group. Additionally, patients were divided into malignant (90) and non-malignant (139) groups based on dysplasia. The polyp group was further divided into malignant (62) and non-malignant (77) groups.\u003c/p\u003e \u003cp\u003eThe study recorded age, gender, history of colorectal polyps, diameter, location, and degree of dysplasia of LSTs and polyps. Serum tumor biomarkers: carcinoembryonic antigen (CEA), cancer antigen (CA)19\u0026thinsp;\u0026minus;\u0026thinsp;9, CA125 were also documented. The study adhered to the ethical guidelines of the Declaration of Helsinki and was approved by the Ethics Committee of the First People's Hospital of Lianyungang (KY-20240528001-01).\u003c/p\u003e \u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eEndoscopic Criteria of LSTs\u003c/h2\u003e \u003cp\u003eLSTs were classified into granular and non-granular types according to the Kudo classification. Granular types include nodular mixed and homogeneous types, while non-granular types include elevated and pseudodepressed types[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. LST locations were categorized as ileocecal region, ascending colon, transverse colon, descending colon, sigmoid colon, and rectum. The right colon includes the cecum, ascending colon, and two-thirds of the transverse colon; the left colon includes one-third of the transverse colon, descending colon, and sigmoid colon.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003eHistopathological Assessment\u003c/h2\u003e \u003cp\u003eThe histopathological type of LST was determined according to the WHO 2010 criteria for digestive tract tumors[\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. Types include hyperplastic, low-grade, high-grade, and carcinoma. High-grade intraepithelial neoplasia and invasive carcinoma were defined as malignant, while hyperplastic and low-grade intraepithelial neoplasia were defined as non-malignant. Pathological types include proliferative polyps, serrated lesions, tubular adenomas, villous tubular adenomas, and adenocarcinoma[\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e, \u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e].\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003eStatistical Analysis\u003c/h2\u003e \u003cp\u003eData were analyzed using SPSS version 24 (SPSS Inc., Chicago, IL, USA). Categorical data were analyzed using the Chi-square test or Fisher's exact test for group comparisons. Normally distributed continuous data were presented as mean\u0026thinsp;\u0026plusmn;\u0026thinsp;standard deviation and assessed using the independent samples t-test. For continuous data not following a normal distribution, the Mann-Whitney U test was employed for between-group comparisons. A two-sided P-value\u0026thinsp;\u0026lt;\u0026thinsp;0.05 indicated statistical significance. Variables with P\u0026thinsp;\u0026lt;\u0026thinsp;0.05 were included in binary logistic regression analysis to identify predictors of LSTs with colorectal polyps and independent risk factors for malignant transformation.\u003c/p\u003e \u003c/div\u003e"},{"header":"Results","content":"\u003cp\u003e\u003cstrong\u003eBaseline Clinicopathological Factors\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eA total of 229 patients were included, with 90 in the non-polyp group and 139 in the polyp group (Table 1). No significant differences were found in the history of colorectal polyps (\u003cem\u003eP\u003c/em\u003e = 0.22), diameter (\u003cem\u003eP\u003c/em\u003e = 0.321), location (\u003cem\u003eP\u003c/em\u003e = 0.547), or morphological type (\u003cem\u003eP\u003c/em\u003e = 0.256) between groups. However, patients aged \u0026ge; 50 years (\u003cem\u003eP\u003c/em\u003e = 0.041) and males (\u003cem\u003eP\u003c/em\u003e \u0026lt; 0.001) were more frequent in the polyp group. Tubular adenomas were the predominant pathological type of LSTs, especially in the polyp group (\u003cem\u003eP\u003c/em\u003e = 0.034). LSTs were more frequently located in the ascending colon(24.9%)and rectum(23.6%). Tumor markers CEA (\u003cem\u003eP\u003c/em\u003e = 0.069), CA199 (\u003cem\u003eP\u003c/em\u003e = 0.598), CA125 (\u003cem\u003eP\u0026nbsp;\u003c/em\u003e= 0.541) were not significantly associated with colon polyps. Binary logistic regression analysis indicated that being male (OR = 0.330, 95%CI: 0.186 - 0.586, \u003cem\u003eP\u003c/em\u003e \u0026lt; 0.001) and aged between 50 and 75 (OR = 4.293, 95%CI: 1.060 - 17.376,\u003cem\u003e\u0026nbsp;P\u003c/em\u003e = 0.041) were predictors of LSTs with colorectal polyps (Table 2). The AUC of the binary logistic model was 0.703 (95% CI 0.633 - 0.773; \u003cem\u003eP\u003c/em\u003e \u0026lt; 0.001) (Figure 1a).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eRisk Factors for Malignant Lesions in LSTs\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003ePatients were divided into non-malignant (139) and malignant (90) groups based on histology. Differences were significant in location (\u003cem\u003eP\u003c/em\u003e \u0026lt; 0.001), diameter (\u003cem\u003eP\u003c/em\u003e \u0026lt; 0.001), the coexistence of colorectal polyps (\u003cem\u003eP\u003c/em\u003e = 0.041), and morphological type (\u003cem\u003eP\u003c/em\u003e \u0026lt; 0.001) between groups (Table 3). No significant differences were found in gender (\u003cem\u003eP\u003c/em\u003e = 0.206) and age (\u003cem\u003eP\u003c/em\u003e = 0.074). Tumor markers CEA \u003cem\u003e(P\u0026nbsp;\u003c/em\u003e= 0.848), CA125 (\u003cem\u003eP\u003c/em\u003e = 0.36) showed no significant differences, but CA199 was significant (\u003cem\u003eP\u003c/em\u003e = 0.003). Binary logistic regression analysis revealed that LSTs with a diameter \u0026gt; 2 cm (OR = 3.757, 95% CI: 1.774 - 7.957, P \u0026lt; 0.001), coexistence with colon polyps (OR = 3.884, 95% CI: 1.794 - 8.407, \u003cem\u003eP\u003c/em\u003e \u0026lt; 0.001), location in the rectum (OR = 3.449, 95% CI: 1.078 - 11.030, \u003cem\u003eP\u003c/em\u003e = 0.037), and LST-G-M (OR = 9.578, 95% CI: 3.937 - 23.301, \u003cem\u003eP\u003c/em\u003e \u0026lt; 0.001), LST-NG-FE (OR = 0.201, 95% CI: 0.056 - 0.719, \u003cem\u003eP\u003c/em\u003e = 0.014) morphological types increased the risk of malignancy (Table 4). The AUC of the binary logistic model was 0.859 (95% CI 0.812 - 0.906; \u003cem\u003eP\u003c/em\u003e \u0026lt; 0.001) (Figure 1b).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eRisk Factors for Malignant Lesions in LSTs Coexisting with Colon Polyps\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eIn the polyp group, patients were divided into non-malignant (77) and malignant (62) groups. Significant differences were found in age (\u003cem\u003eP\u0026nbsp;\u003c/em\u003e= 0.018), location of LST (\u003cem\u003eP\u0026nbsp;\u003c/em\u003e= 0.006), and diameter of LST (\u003cem\u003eP\u0026nbsp;\u003c/em\u003e\u0026lt; 0.001) (Table 5). No significant differences were found in gender (\u003cem\u003eP\u0026nbsp;\u003c/em\u003e= 0.353), polyp location (\u003cem\u003eP\u0026nbsp;\u003c/em\u003e= 0.841), polyp size (\u003cem\u003eP\u0026nbsp;\u003c/em\u003e= 0.139), polyp number (\u003cem\u003eP\u0026nbsp;\u003c/em\u003e= 0.377), distance between polyps and LSTs (\u003cem\u003eP\u0026nbsp;\u003c/em\u003e= 0.804), and pathological types of polyps (\u003cem\u003eP\u0026nbsp;\u003c/em\u003e= 0.102). In the non-malignant group, all polyps were non-malignant, while four polyps in the malignant group were malignant. However, not all histopathological types of polyps were examined and collected. No significant differences were found in CEA (\u003cem\u003eP\u0026nbsp;\u003c/em\u003e= 0.594) and CA125 (\u003cem\u003eP\u0026nbsp;\u003c/em\u003e= 0.362), but CA199 showed a significant difference (\u003cem\u003eP\u0026nbsp;\u003c/em\u003e= 0.002). Binary logistic regression analysis indicated that LSTs with a diameter \u0026ge; 2 cm (OR = 4.574, 95% CI: 1.754 - 11.933, \u003cem\u003eP\u0026nbsp;\u003c/em\u003e= 0.002), LST-G-H (OR = 8.761, 95% CI: 2.788 - 27.530, \u003cem\u003eP\u003c/em\u003e \u0026lt; 0.001), and LST-G-M (OR = 0.182, 95% CI: 0.039 - 0.845, \u003cem\u003eP\u0026nbsp;\u003c/em\u003e= 0.030) were risk factors for malignant transformation in LSTs coexisting with colon polyps (Table 6). The AUC of the ROC curve was 0.873 (95% CI 0.814 - 0.931, \u003cem\u003eP\u0026nbsp;\u003c/em\u003e\u0026lt; 0.001) (Figure 1c).\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eThis study found that patients with LSTs are predominantly male and older, making the presence of colorectal polyps more likely. However, these two factors did not increase the malignancy risk of LSTs. Surprisingly, when further assessing the malignancy risk of LSTs coexisting with colorectal polyps, it was found that being male still did not increase the malignancy risk, but univariate analysis showed that age did increase the risk of malignancy. Previous studies [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e, \u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]have indicated that LST patients are typically around 65 years old and predominantly male, similar to our study. In a retrospective study by Shen[\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e], the risk of coexisting colorectal polyps and LSTs increased in males and individuals aged 50 to 75, but this did not increase the malignancy risk of LSTs. Other studies [\u003cspan additionalcitationids=\"CR20\" citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e]have pointed out that male gender and advanced age are risk factors for colorectal polyps, which explains the significant differences observed in our study when LSTs coexist with polyps, but further research is needed to determine whether advanced age increases the malignancy risk of LSTs.\u003c/p\u003e \u003cp\u003eNext, does the diameter of LSTs increase their malignancy risk? A meta-analysis indicated that larger LSTs have a higher incidence of submucosal invasive cancer. Specifically, the incidence rates of submucosal invasive cancer for LSTs with diameters of 10\u0026ndash;19 mm, 20\u0026ndash;29 mm, and greater than 30 mm are 4.6%, 9.2%, and 16.5%, respectively[\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e]. Our study found that LSTs with a diameter greater than 2 cm are a risk factor for malignant transformation, regardless of the coexistence with colorectal polyps.\u003c/p\u003e \u003cp\u003eThis study found that tubular adenoma is the most common pathological type of LSTs. Kyeong's research also supports this view, excluding LST-NG-PD[\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e]. In this study, the distribution of LST subtypes was 64 cases (27.9%) of LST-G-H, 87 cases (38.0%) of LST-G-M, 57 cases (24.9%) of LST-NG-FE, and 21 cases (9.2%) of LST-NG-PD. Previous studies[\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e] have also reported that granular types account for 68.1% of LSTs, with LST-G-M comprising 38%; non-granular types account for 39.2%, with LST-NG-PD comprising 15.2%.\u003c/p\u003e \u003cp\u003eSerum tumor markers are valuable adjunctive tools for the diagnosis and prognosis assessment of colorectal cancer (CRC). Liu's meta-analysis reports[\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e] that the sensitivity and specificity of carcinoembryonic antigen (CEA) for diagnosing CRC are 46% and 89%, respectively. In contrast, carbohydrate antigen 19\u0026thinsp;\u0026minus;\u0026thinsp;9 (CA199) demonstrates a lower sensitivity of approximately 30% but a higher specificity of 92%. Recent research indicates that the combined use of multiple tumor markers may enhance diagnostic and prognostic accuracy[\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e]. Our study observed that CA199 levels were elevated in the malignant group compared to the non-malignant group, irrespective of the presence of colonic polyps. However, due to the limited dataset, these findings should be considered preliminary, and further studies with larger sample sizes are warranted to validate these results.\u003c/p\u003e \u003cp\u003eWe further investigated the impact of LST surface morphological subtypes on malignancy risk. This study found that the malignant group had more patients with LST-G-M and LST-NG-PD, while the non-malignant group had more patients with LST-G-H and LST-NG-FE. Multiple studies [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e, \u003cspan additionalcitationids=\"CR28\" citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e]have found that precancerous lesions and submucosal cancer are more apparent in nodular mixed tumors within the granular type than in homogeneous tumors; in the non-granular type, pseudo-depressed tumors are more common than flat elevated tumors. Kudo's research[\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e] indicated that LST-NG-PD has a higher invasion rate. Our further findings suggested that when coexisting with colorectal polyps, the LST subtype LST-G-H reduces the malignancy risk, but when not considering coexistence, LST-NG-FE reduces the malignancy risk. This might be due to the small sample size, and further studies with larger samples are needed. This suggests that the endoscopic classification of LSTs is a predictor of malignancy.\u003c/p\u003e \u003cp\u003eWe also evaluated the impact of LST location on malignancy risk. Studies from Japan and Italy have shown that LSTs are mostly located in the proximal colon[\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e]. However, other studies [\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e, \u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e]have pointed out that granular lesions are most commonly found in the rectum and proximal colon, whereas non-granular lesions are most commonly found in the transverse colon. In this study, 53.3% (122/229) of LSTs were located in the proximal colon, but in the malignant group, LSTs were mostly located in the distal colon, particularly the rectum. Yusuke Horiuchi's research [\u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e]indicated that rectal LST-NG-PD tumors have a high proportion of submucosal invasive lesions, and non-granular tumors, whether LST-NG-PD or LST-NG-FE, located in the rectum may have higher malignancy than those in the colon. Other studies have reported that invasive cancer is rarely found in LST-G-H lesions[\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e, \u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e, \u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e]. This study found that in the evaluation of LST location, the rectum had the highest proportion at 40%; when coexisting with colorectal polyps, it was 36.5%; and it remained significant in multivariate analysis, while there was no significant difference in coexisting with colon polyps. This has clinical implications, suggesting that when LSTs are located in the rectum, the possibility of malignancy increases.\u003c/p\u003e \u003cp\u003eThe coexistence of colorectal polyps and LSTs is common. Previous studies[\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e] have pointed out that right colon polyps are the most important risk factor for predicting the malignancy of LSTs. Our study indicated that the coexistence of colorectal polyps increases the malignancy risk of LSTs, but the location and pathological morphology of colorectal polyps are not significant in the assessment, possibly due to the multiplicity of colorectal polyps, making complete statistics challenging.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eWhen performing colonoscopy, endoscopists can assess the malignancy risk of LSTs based on the coexistence with colorectal polyps, the diameter of LSTs, the surface morphology, and the location of LSTs. However, age may increase the malignancy risk of LSTs when coexisting with colorectal polyps. For high-risk LST lesions, active endoscopic treatment should be pursued to reduce the occurrence of colorectal malignancies. This study primarily investigates the clinical characteristics and malignancy risk assessment of LSTs coexisting with colorectal polyps. Future studies can explore the clinical characteristics and malignancy risk assessment of LSTs in different locations or morphological types to further guide clinical practice.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e \u003ch2\u003eAuthor contributions statement\u003c/h2\u003e \u003cp\u003eQingwen Yuan, Xuyang Liang and Jiafu Song designed the study. Zhimei Zhang, Yanqi Zhang and Shuxian Zhang collected data. Chenyan Zuo and Huahui Zhang analyzed the data and prepared the manuscript. Qingwen Yuan and Yanqi Zhang directed final version of all contents. All authors reviewed and approved the manuscript.\u003c/p\u003e \u003c/p\u003e\u003cp\u003e \u003ch2\u003eDeclaration of competing interest\u003c/h2\u003e \u003cp\u003eThe authors declare no conflict of interest.\u003c/p\u003e \u003c/p\u003e\u003ch2\u003eFunding\u003c/h2\u003e \u003cp\u003eThis work was supported by the Early Gastrointestinal Cancer Program (GTCZ-2022-JS-32-0002)\u003c/p\u003e\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\u003cp\u003eQ.W. Y., X.Y. L. and J.F.S. designed the study. Z.M.Z., Y.Q. Z. and S. X.Z. collected data. C.Y.Z. and H.H.Z. analyzed the data and prepared the manuscript. Q.W. Y. and Y.Q.Z. directed final version of all contents. All authors reviewed and approved the manuscript.\u003c/p\u003e\u003ch2\u003eAcknowledgement\u003c/h2\u003e\u003cp\u003eThe authors thank Ying Zhou for her assistance with language and the reviewers for allowing us to make improvements to the manuscript\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eVlad Alexandru I, Gina G, Nicolae B, Alexandru Laurentiu C, Camelia DJM. Colorectal Cancer: From Risk Factors to Oncogenesis. Medicina (Kaunas) 2023;59(9).https://dx.doi.org/10.3390/medicina59091646\u003c/li\u003e\n\u003cli\u003eB J R, T F, A C, M F D, S Y, D M C et al. Flat and depressed colonic neoplasms: a prospective study of 1000 colonoscopies in the UK. Lancet. 2000;355(9211):1211-4.https://dx.doi.org/10.1016/s0140-6736(00)02086-9\u003c/li\u003e\n\u003cli\u003eRoy S, Shai F, Tonya K, Kazuaki C, Shinji TJG. Nonpolypoid (flat and depressed) colorectal neoplasms. Gastroenterology. 2006;130(2):566-76; quiz 88-9. https://dx.doi.org/10.1053/j.gastro.2005.12.006\u003c/li\u003e\n\u003cli\u003eS J W, A G Z, M N H, M J OB, L S G, S S S et al. Prevention of colorectal cancer by colonoscopic polypectomy. The National Polyp Study Workgroup. New England Journal of Medicine. 1993;329(27):1977-81.https://dx.doi.org/10.1056/nejm199312303292701\u003c/li\u003e\n\u003cli\u003eShin ei K, Ren\u0026eacute; L, John I A, Hiroaki F, Takahiro F, Hiroshi K et al. Nonpolypoid neoplastic lesions of the colorectal mucosa. Gastrointestinal Endoscopy. 2008;68(0):S3-47. https://dx.doi.org/10.1016/j.gie.2008.07.052\u003c/li\u003e\n\u003cli\u003eY O, T T, T O, S H, H MJJGH. Laterally spreading tumor: clinicopathological study in comparison with the depressed type of colorectal tumor. Journal of Gastroenterology and Hepatology. 2001;16(7):770-6. https://dx.doi.org/10.1046/j.1440-1746.2001.02512.x\u003c/li\u003e\n\u003cli\u003eS KJE. 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Proportion of flat- and depressed-type and laterally spreading tumor among advanced colorectal neoplasia. Clinical Gastroenterology and Hepatology. 2011;9(6):503-8.https://dx.doi.org/10.1016/j.cgh.2011.03.018\u003c/li\u003e\n\u003cli\u003eKiyonori K, Shinji T, Yoshitaka M, Hideki I, Miwa S, Shiro O et al. Predictors of invasive cancer of large laterally spreading colorectal tumors: A multicenter study in Japan. JGH Open. https://dx.doi.org/10.1002/jgh3.12222\u003c/li\u003e\n\u003cli\u003eXiao-Wen H, Peng L, Yong-Jun W, Ming J, Shu-Tian Z, Hai-Yun SJWJGO. Predictors for malignant potential and deep submucosal invasion in colorectal laterally spreading tumors. World Journal of Gastrointestinal Oncology. 2022;14(7):1337-47.https://dx.doi.org/10.4251/wjgo.v14.i7.1337\u003c/li\u003e\n\u003cli\u003eXiaonan S, Yao Z, Yunjia Z, Xiaobo L, Zhizheng G, Hua X et al. The Coexistence of Colorectal Polyps in the Right Colon Increases the Malignant Risk of Laterally Spreading Tumors. Gastroenterology Research and Practice. 2020;2020(0):3180420. https://dx.doi.org/10.1155/2020/3180420\u003c/li\u003e\n\u003cli\u003eJiaqi P, Li C, Lei X, Min M, Youming L, Chaohui Y et al. Prevalence and risk factors for colorectal polyps in a Chinese population: a retrospective study. Scientific Reports. 2020;10(1):6974. https://dx.doi.org/10.1038/s41598-020-63827-6\u003c/li\u003e\n\u003cli\u003eKyujin L, Yong Hwan KJIJERPH. Colorectal Polyp Prevalence According to Alcohol Consumption, Smoking and Obesity. International Journal of Environmental Research and Public Health. 2020;17(7). https://dx.doi.org/10.3390/ijerph17072387\u003c/li\u003e\n\u003cli\u003eJin X, Wei H, Nannan Z, Nan S, Junning ZJAPM. Risk factors and correlation of colorectal polyps with type 2 diabetes mellitus. Annals of Palliative Medicine. 2022;11(2):647-54.https://dx.doi.org/10.21037/apm-21-3943\u003c/li\u003e\n\u003cli\u003eAndreas P, Alanna E, Bruno M, Tina S, Matthias A, Carola F et al. Endoscopic submucosal dissection for early rectal neoplasia: experience from a European center. Endoscopy 2016;49(3):222-32. https://dx.doi.org/10.1055/s-0042-118449\u003c/li\u003e\n\u003cli\u003eKyeong Ok K, Byung Ik J, Woo Jin J, Si Hyung LJIJCD. Laterally spreading tumors of the colorectum: clinicopathologic features and malignant potential by macroscopic morphology. International Journal of Colorectal Disease. 2013;28(12):1661-6. https://dx.doi.org/10.1007/s00384-013-1741-6\u003c/li\u003e\n\u003cli\u003eB C K, H J C, K Su H, D K S, C W H, J W P et al. Clinicopathological differences of laterally spreading tumors of the colorectum according to gross appearance. Endoscopy. 2010;43(2):100-7.https://dx.doi.org/10.1055/s-0030-1256027\u003c/li\u003e\n\u003cli\u003eZhongyu L, Yingchong Z, Yulong N, Ke L, Xin L, Huijuan C et al. A systematic review and meta-analysis of diagnostic and prognostic serum biomarkers of colorectal cancer. PLoS One 2014;9(8):e103910. https://dx.doi.org/10.1371/journal.pone.0103910\u003c/li\u003e\n\u003cli\u003eHai L, Kexin S, Bo L, Ruiqi L, Zeming W, Zhongshi XJOL. Clinical significance and diagnostic value of serum NSE, CEA, CA19-9, CA125 and CA242 levels in colorectal cancer. Oncology Letters. 2020;20(1):742-50. https://dx.doi.org/10.3892/ol.2020.11633\u003c/li\u003e\n\u003cli\u003eB C K, H J C, K Su H, D K S, C W H, J W P et al. Clinicopathological differences of laterally spreading tumors of the colorectum according to gross appearance. 2010;43(2).https://dx.doi.org/10.1055/s-0030-1256027\u003c/li\u003e\n\u003cli\u003eTomoya S, Kiyonori K, Miwa S, Yasuhiro M, Miyuki M, Kana K et al. Comparison of the histopathological characteristics of large colorectal laterally spreading tumors according to growth pattern. Journal of the Anus, Rectum and Colon. 2019;3(4):152-9.https://dx.doi.org/10.23922/jarc.2018-036\u003c/li\u003e\n\u003cli\u003eRoel M M B, Manon H J V, Luc A R S S, Bjorn W, Tonya K, Ad A M M et al. Endoscopic subtypes of colorectal laterally spreading tumors (LSTs) and the risk of submucosal invasion: a meta-analysis. Endoscopy. 2017;50(3):263-82.https://dx.doi.org/10.1055/s-0043-121144\u003c/li\u003e\n\u003cli\u003eShin-ei K, Orie T, Kazuo OJGECNA. Flat and depressed types of early colorectal cancers: from East to West. Gastrointestinal Endoscopy Clinics of North America. 2008;18(3):581-93.https://dx.doi.org/10.1016/j.giec.2008.05.013\u003c/li\u003e\n\u003cli\u003eRen\u0026eacute; L, Shinji TJEJGH. Laterally spreading tumors in the colon and rectum. European Journal Of Gastroenterology \u0026amp; Hepatology. 2012;24(10):1123-34.https://dx.doi.org/10.1097/MEG.0b013e328355e2d9\u003c/li\u003e\n\u003cli\u003eHitoshi N, Hajime I, Naoyuki Y, Hiroyuki I, Eiichiro F, Haruhisa M et al. Endoscopic submucosal dissection for laterally spreading tumours of the colorectum in 200 consecutive cases. Surgical Endoscopy. 2010;24(11):2881-7.https://dx.doi.org/10.1007/s00464-010-1071-5\u003c/li\u003e\n\u003cli\u003eYusuke H, Akiko C, Yasumasa M, Teruhito K, Naoyuki U, Yoshiya F et al. Diagnosis of laterally spreading tumors (LST) in the rectum and selection of treatment: characteristics of each of the subclassifications of LST in the rectum. Digestive Endoscopy. 2013;25(6):608-14. https://dx.doi.org/10.1111/den.12040\u003c/li\u003e\n\u003cli\u003eY S, T F, H K, H M, T Y, T K et al. Endoscopic treatment for laterally spreading tumors in the colon. Endoscopy. 2001;33(8):682-6. https://dx.doi.org/10.1055/s-2001-16213\u003c/li\u003e\n\u003cli\u003eShiro O, Shinji T, Hiroyuki K, Sayaka O, Kazuaki CJDE. Therapeutic strategy for colorectal laterally spreading tumor. Digestive Endoscopy. 2009(0):S43-6.https://dx.doi.org/10.1111/j.1443-1661.2009.00869.x\u003c/li\u003e\n\u003c/ol\u003e"},{"header":"Tables","content":"\u003cp\u003eTables 1-6 are available in the Supplementary Files section.\u003c/p\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"
[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Laterally spreading tumor, Colorectal cancer, Colorectal Polyps, Malignant risk","lastPublishedDoi":"10.21203/rs.3.rs-4611935/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-4611935/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003ePurpose\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eLateral spreading tumors (LSTs) and colorectal polyps are both considered precursors to colorectal cancer and often coexist. This study aimed to identify independent predictive factors for the coexistence of LSTs with colorectal polyps and the independent risk factors for malignancy in LSTs with colorectal polyps.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis retrospective study included 229 patients diagnosed with LSTs via colonoscopy at Lianyungang First People's Hospital from January 2020 to March 2024. Patients were divided into two groups based on the presence of colorectal polyps: polyp group (n = 139) and non-polyp group (n = 90). Clinicopathological characteristics were compared between the two groups, and binary logistic regression was used to identify predictive factors for coexistence. The polyp group was further subdivided into malignant group (n = 62) and non-malignant group (n = 77) based on the degree of dysplasia. Binary logistic regression was also used to analyze the risk factors for malignant transformation of LSTs with colorectal polyps.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eMale gender (OR = 0.330, 95% CI: 0.186 - 0.586, \u003cem\u003eP \u003c/em\u003e\u0026lt; 0.001) and age between 50 - 75 years (OR = 4.293, 95% CI: 1.060 - 17.376, \u003cem\u003eP \u003c/em\u003e= 0.041) were identified as predictive factors for the coexistence of colorectal polyps with LSTs. The area under the receiver operating characteristic curve (AUC) for the predictive model was 0.703 (95% CI: 0.633 - 0.773; \u003cem\u003eP \u003c/em\u003e\u0026lt; 0.001). LST diameter ≥ 2 cm (OR = 4.574, 95% CI: 1.754 - 11.933, \u003cem\u003eP \u003c/em\u003e= 0.002), LST-G-H subtype (OR = 8.761, 95 % CI: 2.788 - 27.530, \u003cem\u003eP \u003c/em\u003e\u0026lt; 0.001), and LST-G-M subtype (OR = 0.182, 95%CI: 0.039 - 0.845, \u003cem\u003eP \u003c/em\u003e= 0.030) were identified as risk factors for malignant transformation of LSTs with colorectal polyps. The AUC for this predictive model was 0.873 (95% CI: 0.814 - 0.931, \u003cem\u003eP \u003c/em\u003e\u0026lt; 0.001).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusion\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eMen aged 50 - 75 with LSTs are more likely to have coexisting colorectal polyps. Larger LST diameter and mixed nodular subtype increase the risk of malignant transformation when coexisting with colorectal polyps, whereas homogeneous granular subtype may reduce this risk.\u003c/p\u003e","manuscriptTitle":"Predictive Factors for the Coexistence of Colorectal Lateral Spreading Tumors and Colorectal Polyps, and Risk Factors for Malignant Transformation","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-07-18 20:34:40","doi":"10.21203/rs.3.rs-4611935/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"
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