Pathological features and risk factors for submucosal infiltration of colorectal lateral spreading tumors

Abstract

BACKGROUND

To observe the endoscopic and pathological characteristics of laterally spreading tumors (LSTs) and explore the risk factors for carcinogenesis and submucosal infiltration.

AIM

To analyze the clinicopathological features of colorectal LSTs treated endoscopically and determine risk factors associated with carcinogenesis and submucosal invasion, providing evidence-based guidance for optimal treatment strategy selection.

METHODS

This study retrospectively analyzed the sex, age, and endoscopic and pathological features of patients who underwent endoscopic treatment for colorectal LSTs in our hospital from January 2021 to July 2024. Single-factor analysis was used to identify the risk factors for cancer and submucosal infiltration, and the factors with statistical significance were included in multivariate logistic regression analysis.

RESULTS

A total of 422 patients, including 224 males and 198 females, aged 63.45 ± 9.23 years, were included. There were 456 LST lesions in total. The length of the endoscopically resected specimens was 3.01 ± 0.48 cm, and the length of the lesions was 2.37 ± 1.59 cm. It was located in 115 rectums (25.2%), 40 sigmoid colon (8.8%), 26 descending colon (5.7%), 109 transverse colon (23.9%), 112 ascending colon (24.6%), and 54 ileocecal regions (11.8%). Endoscopic submucosal dissection (ESD) was performed in 237 patients (52.0%), and endoscopic mucosal resection (EMR) was performed in 95 patients (20.8%). There were 113 EMR with precutting cases (24.8%), 11 ESD with snare cases (2.4%), 4 delayed bleeding cases and 5 intraoperative perforations. The pathological results revealed 119 cases of low-grade intraepithelial neoplasia (26.1%), 221 cases of high-grade intraepithelial neoplasia (48.5%), 82 cases of intramucosal carcinoma (18.0%), and 34 cases of submucous invasive carcinoma (7.5%). Multiple logistic regression analyses revealed that lesion size ( > 2 cm), lesion location (rectal) and endoscopic classification [false depressed tubulovillous adenoma (LST-NG pseudodepressed type, LST-NG-PD), type 1 particles (LST-G homogenous type), and LST-G nodular mixed type], accompanied by large nodules (with) were independent risk factors for carcinogenesis; endoscopic classification (LST-NG-PD) and the presence of large nodules were independent risk factors for submucosal infiltration.

CONCLUSION

These risk factors provide practical guidance for treatment selection: LST-NG-PD with large nodules should prioritize ESD, while high-risk rectal lesions > 2 cm may require additional imaging evaluation before endoscopic resection.

Key Words: Colorectal tumor; Tumor infiltration; Lateral developmental tumor; Endoscopic submucosal dissection; Endoscopic mucosal resection

Core Tip: This study investigates the endoscopic and pathological characteristics of laterally spreading tumors (LSTs) in the colon and rectum, focusing on the risk factors for carcinogenesis and submucosal infiltration. The results highlight that lesion size, location, and endoscopic classification, particularly the presence of large nodules, are independent risk factors for malignant transformation. Additionally, the endoscopic classification of LST-NG pseudodepressed type, along with large nodules, is a significant predictor of submucosal infiltration. The study emphasizes the importance of careful endoscopic evaluation for early detection and appropriate treatment strategies, including endoscopic submucosal dissection and mucosal resection.

INTRODUCTION

The concept of laterally spreading tumors (LSTs), proposed by Japanese scholar Shinji Kudo in 1993, refers to a class of lesions that originate from the mucosa of the large intestine and grow laterally along the surface of the intestinal mucosa with a diameter of > 1 cm. In terms of morphology, LSTs are morphologically classified into two main categories: Granular type (LST-G) and nongranular type (LST-NG). LST-G lesions exhibit granular or nodular surfaces, while LST-NG lesions present with smooth, flat surfaces[1-3]. LST-G is further subdivided into homogenous type (LST-G-H), characterized by uniformly distributed surface granules, and nodular mixed type (LST-G-M), which displays irregular nodular architecture with heterogeneous surface morphology[4-6]. LST-NG can be divided into the LST-NG flat-elevated type (LST-NG-F) and the LST-NG pseudodepressed type (LST-NG-PD). The former has a flat tumor surface and no depression[7-9]. The latter tumor has an ill-defined central depression. Most of the histopathological types of LSTs are adenomas, which have the potential for malignant transformation and need intervention treatment[10]. Because LSTs mainly grow laterally and superficially along the mucosal surface, the risk of deep invasion into the intestinal wall is low, so endoscopic treatment is suitable. Endoscopic mucosal resection (EMR) and endoscopic submucosal dissection (ESD) are the main EMR methods[11-13]. The EMR procedure is simple, and the operation time is short. However, for large-diameter lesions, the whole piece cannot be removed, which easily leads to residual lesions and the recurrence of local lesions[14-16]. Although full resection of large lesions can be achieved via ESD, the operation is difficult, the operation time is long, and the complication rate is high. In recent years, improved methods for the above two endoscopic resection methods have emerged, namely, EMR with precutting (EMR-P) and ESD with a snare (ESD-S). The literature reports that these two improved endoscopic resection methods each have special advantages[17-20].

The pathological type of LST is usually adenoma, carcinoma with a mucosal layer or superficial submucosal infiltration. Endoscopic treatment has good curative effects and can achieve curative resection. Therefore, if the pathological type and infiltration depth of the LST can be accurately evaluated through colonoscopy and if appropriate endoscopic treatment can be selected, unnecessary surgical operations can be avoided. The purpose of this study was to summarize the endoscopic characteristics of colorectal LSTs treated via endoscopy at our center, analyze the risk factors for LST cancer and submucosal invasion, and compare the advantages and disadvantages of different endoscopic treatment methods.

MATERIALS AND METHODS

Patient selection

We retrospectively analyzed the data of 422 patients (456 lesions) who underwent endoscopic treatment for colorectal LSTs in our hospital from January 2021 to July 2024. The collected information included patients' basic information (gender, age), endoscopic characteristics (lesion size, location, and endoscopic type), treatment status (endoscopic treatment method, operation time, and complications), postoperative pathological results and follow-up results. The inclusion criteria were as follows: Patients whose colorectal lesions were LSTs and whose clinical, endoscopic and pathological data were complete. Patients with incomplete endoscopic resection or in situ recurrence were excluded. No contraindications for endoscopic therapy were found in the preoperative evaluation of all patients, and informed consent for endoscopic therapy was signed.

Endoscopic therapy

Before the operation, the patient was evaluated by anesthesia, an intubated tracheal tube or intravenous general anesthesia, and the scope was transferred to the lesion position in the lateral or supine position.

Endoscopy procedure: (1) EMR: A mixture of normal saline and methylene blue was injected under the mucosa around the lesion. After the lesion was fully lifted, it was resected with a snare; (2) EMCR-P: A mixture of normal saline and methylene blue solution was injected under the surrounding mucosa, the circumferential mucosa was cut along the lesion margin with a Dual knife, the lesion was injected under the lesion base mucosa according to the situation, and then the lesion was resected with a snare; (3) ESD: A mixture of normal saline and methylene blue solution was injected under the mucosa surrounding the lesion, a dual knife was used to cut the surrounding mucosa circumferentially, and then the lesion was gradually peeled under the mucosa until the lesion was completely removed; and (4) ESD-S: A mixture of normal saline and methylene blue solution was injected under the surrounding mucosa, and the surrounding mucosa was circumvented or partially circumvented with a dual knife; then, the lesion was gradually removed from the submucosa. After the partial lesion was removed, the lesion was resected with a snare. All endoscopic procedures were performed by senior endoscopists with over 5 years of ESD/EMR experience and a minimum of 100 colorectal ESD cases performed annually. Magnification endoscopy with narrow-band imaging (NBI) was routinely utilized for LST characterization and pit pattern analysis according to JNET classification criteria. To minimize interobserver variability, LST morphological classification was independently assessed by two experienced endoscopists, with disagreements resolved through consensus discussion with a third senior endoscopist. All resected specimens underwent pathological review by two expert gastrointestinal pathologists. In cases of diagnostic discrepancy (n = 23, 5.1%), consensus was achieved through joint microscopic examination and collaborative discussion to ensure diagnostic consistency and accuracy.

Pathological evaluation

Specimen pretreatment: (1) Fully extend the sample to maintain the integrity of the lesion. A thin needle is used to secure the excised specimen on a foam or rubber plate at the edge to fully extend the sample and maintain the integrity of the lesion. Notably, the degree of specimen extension is commensurate with the physiological state of the lesion itself and should not be excessively stretched because it may affect pathological observation. The relative position of the specimen in the body around the specimen, such as the oral side, anal side, left side, right side, anterior wall, and posterior wall, was marked so that the pathologist could identify the position of the specimen. The endoscopist marked the high-risk areas found in the preoperative diagnosis and communicated with the pathologist; and (2) Fix the sample in time to avoid drying the sample. The specimens should not be exposed in vitro for too long because excessive drying will cause morphological changes in the mucosal epithelium, resulting in deviations in pathological diagnosis. The samples were soaked in 4% formalin (40% formaldehyde solution) in time, and more than 10 times the volume of each sample was fixed for 6-48 hours.

Pathological sampling of the samples: (1) Specimen check. Check name, gender, medical record number, etc.; (2) Take pictures. Images were taken before and after the tissue sampling knife. The position relationship between the lesion and the surrounding normal mucosa was recorded by the film taken before specimen dissection. The film taken after the incision is convenient for pathological diagnosis of the mucosal lesions in different areas, the severity of the lesions and the spatial position relationship of the sample; (3) General inspection and records. The specimen size and lesion size, gross classification, and distance of the lesion from the four incisal edges were measured and recorded. In complex specimens, attention should be given to clinical and pathological communication to map specimen extension and reconstruction; and (4) Draw materials. All EMR/ESD excision samples were collected. The sampling principle is perpendicular to the nearest lateral incisal edge. The mucosal lateral incisal margin and the basal incisal margin can be marked with ink or carbon ink (if possible, different colors can be painted on the oral side and anal side for identification) to locate the incisal margin under the microscope and evaluate the tumor incisal margin. First, the incisal edge nearest to the lesion was determined. The incisal edge was taken as the reference point, and the incision was made perpendicular to the tangent direction. The knife was cut 1 mm from the side of the incisal edge nearest to the lesion, and the incision was made in parallel every 2 to 3 mm. Pathologists evaluated lesion size, histological type, depth of infiltration, incisal margin, and vascular infiltration. Lesion size was determined by measuring the maximum diameter of the tumor on the resected specimen after proper extension and fixation. The endoscopic resected specimen length refers to the total diameter of the excised tissue, while lesion size specifically represents the maximum tumor diameter within the specimen.

Postoperative treatment and follow-up

After the operation, the patient was deprived of water, intravenous fluids and antibiotics to prevent infection. The patient's vital signs and defecation were observed. The patients in this study were followed up for at least 1 year, and the colonoscopy results were reviewed at 3, 6 and 12 months after surgery and then once a year.

Statistical analysis

SPSS 25.0 statistical software was used to compare and analyze the collected data. The normally distributed data are expressed as mean ± SD values, and analysis of variance was used for comparisons. The nonnormally distributed data are expressed as the M (range), and comparisons were conducted via the rank sum test. Count data are expressed as frequencies (rates), and comparisons were made via the χ² test. Multivariate logistic regression analysis was used to analyze risk factors. P < 0.05 was considered statistically significant.

RESULTS

General clinical data

This study included 422 patients with LSTs, including 456 Lesions. The patients were 63.45 ± 9.23 years old, with 224 males (53.1%) and 198 females (46.9%). The specimen diameter was 3.01 ± 0.48 cm, and the lesion diameter was 2.37 ± 1.59 cm, of which 270 Lesions were ≤ 2 cm (59.2%), 96 Lesions were > 2-3 cm (21.1%), 38 lesions were > 3-4 cm (8.3%), and 30 Lesions were > 4-5 cm (6.6%). Twenty-two cases (4.8%) were > 5 cm. Most of the lesions were located in the rectum, ascending colon, or transverse colon. There were 456 lesions in 115 rectums (25.2%), 40 sigmoid colon (8.8%), 26 descending colon (5.7%), 109 transverse colon (23.9%), 112 ascending colon (24.6%), and 54 ileocecal regions (11.8%). Among the four subtypes of LST, LST-G-M accounted for more than half of the total 262 (57.5%), 77 of which were large nodules (≥ 1 cm). LST-G-H 27 (5.9%); LST-NG-F 109 (23.9%); LST-NG-PD 58 (12.7%). Endoscopic treatment methods included ESD in 237 patients (52%), EMR in 95 patients (20.8%), EMR-P in 113 patients (24.8%), and ESD-S in 11 patients (2.4%). The pathological results revealed 119 cases of low-grade intraepithelial neoplasia (26.1%), 221 cases of high-grade intraepithelial neoplasia (48.5%), 82 cases of intramucosal carcinoma (18.0%), and 34 cases of submucosal infiltrating carcinoma (7.5%). There were 27 SM1 sites and 7 SM2 sites associated with submucosal infiltrating carcinoma.

Comparison of the endoscopic and pathological features of different subtypes of LST

There were 262 LST-G-M sites (57.5%), the specimen size (3.43 ± 1.92) cm, the length of the lesions (2.77 ± 1.72) cm, and the rectum [99 sites (37.8%)], followed by the ascending colon [62 sites (23.7%)]. There were 27 LST-G-H sites (5.9%), the specimen size was 3.58 ± 2.76 cm, the length of the lesion was 2.83 ± 2.54 cm, and the lesions were located mainly in the right half of the colon, 10 ileocecal sites (37.0%), and 9 ascending colon sites (33.3%). LST-NG-F 109 sites (23.9%), specimen size (2.12 ± 1.02) cm, length of lesions (1.64 ± 0.68) cm, transverse colon most [48 (44.0%)], and ascending colon second [28 (25.7%)] were used. There were 58 LST-NG-PD sites (12.7%), the specimen size was 2.48 ± 1.06 cm, and the length of the lesions was 1.79 ± 0.78 cm. The transverse colon had the most lesions [21 sites (36.2%)], followed by the ascending colon [13 sites (22.4%)]. The cancer rate of LST-NG-PD was the highest (37.93%), followed by those of LST-G-M (32.82%), LST-G-H (18.51%), and LST-NG-F (2.75%), as shown in Table 1.

Table 1 Clinical and pathological characteristics of different endoscopic subtypes of lateral developing tumors at 456 locations.

Project	LST-NG-F (n = 109)	LST-NG-PD (n = 58)	IST-G H (n = 27)	LST GM (n = 262)
Lesion size
1-2 cm	93	45	15	117
> 2-3 cm	13	8	5	70
> 3-4 cm	1	5	2	30
> 4-5 cm	2	0	2	26
> 5 cm	0	0	3	19
Location of lesion
Rectum	8	5	3	99
Sigmoid colon	10	8	0	22
Descending colon	10	7	1	8
Transverse colon	48	21	4	36
Ascending colon	28	13	9	62
Cecum	5	4	10	35
Pathologic diagnosis
LGIN	62	12	8	37
HGIEN	44	24	14	139
Mucosal layer cancer	2	12	4	64
Submucosal carcinoma	1	10		22

LST: Lateral developing tumors.

Comparison of the clinical results of different endoscopic treatment methods

The results of the χ² test for descriptive variables and ANOVA for continuous variables revealed that the number of lesions in the ESD, ESD-S, EMR and EMR-P groups was 237, 11, 95 and 113, respectively, and there was no statistically significant difference in age among all groups (F = 2.193, P > 0.05). There was no significant difference in the sex ratio among the groups (χ² = 6.178, P > 0.05). The lesion diameters of the four groups were 3.17 ± 1.83 cm, 2.07 ± 0.77 cm, 1.31 ± 0.36 cm, and 1.65 ± 0.50 cm, respectively, and the differences were statistically significant (F = 213.792, P < 0.001). The operation times of the four groups were 73.40 ± 57.17 minutes, 41.36 ± 28.12 minutes, 8.97 ± 9.04 minutes, and 20.18 ± 9.47 minutes, respectively, and the differences were statistically significant (F = 300.595, P < 0.001). The total removal rates of the four groups were 99.6% (236 sites), 90.9% (10 sites), 95.8% (91 sites), and 97.3% (110 sites), and the difference was statistically significant (χ² = 7.98, P < 0.05). Regarding post-procedural complications, in addition to the previously reported delayed bleeding in 4 cases (0.9%) and intraoperative perforation in 5 cases (1.1%), we identified 2 cases (0.4%) of mild rectal stenosis, both occurring in large rectal lesions with diameter > 3 cm. The stenosis developed within 4-6 weeks post-resection and was successfully treated with endoscopic balloon dilation. Complete symptom resolution was achieved after 2-3 dilation sessions, with no cases requiring surgical intervention. The overall complication rate was 2.4% (11/456 Lesions), confirming the safety and feasibility of endoscopic resection for colorectal LSTs.

Analysis of risk factors for cancer and submucosal infiltration

Low-grade intraepithelial neoplasia and high-grade intraepithelial neoplasia were included in the noncancer group, and intramucosal carcinoma and submucosal infiltrating carcinoma were included in the cancerous group (0 = noncancerous group, 1 = cancerous group). The results of univariate logistic regression analysis revealed that lesion size, location, endoscopic classification and macronodules were relevant factors for carcinogenesis (all P < 0.05). Statistically significant variables in the univariate analysis (and adjusted for confounders) were selected for the multivariate unconditional logistic regression model, and the independent variables were screened by the entry method. The results revealed that lesion size (> 2 cm), lesion location (rectum), endoscopic classification (LST-NG-PD, LST-G-H and LST-G-M) and macronodules (with) were independent risk factors for carcinogenesis (P < 0.05), as shown in Tables 2 and 3.

Table 2 Univariate logistic regression analysis of risk factors for malignant transformation of colorectal lateral developing tumors, n (%).

Project	Non cancerous group (n = 340)	Cancer group (n = 116)	χ2 value	P value
Gender			3.706	0.054
Male	173 (50.9)	71 (61.2)
Female	167 (49.1)	45 (38.8)
Age			1.820	0.177
≤ 64	180 (52.9)	53 (45.7)
> 64	160 (47.1)	63 (54.3)
Disease size			45.072	< 0.001
≤ 2 cm	232 (68.2)	38 (32.8)
> 2 cm	108 (31.8)	78 (67.2)
Location of lesion			51.821	< 0.001
Cecum	50 (14.7)	4 (3.4)
Ascending colon	89 (26.2)	23 (19.8)
Transverse colon	94 (27.6)	15 (12.9)
Descending colon	20 (5.9)	6 (5.2)
Sigmoid colon	28 (8.2)	12 (10.3)
Rectum	59 (17.4)	56 (48.3)
Endoscopic classification			42.566	< 0.001
LST-NG-F	106 (31.2)	3 (2.6)
LST-NG-PD	36 (10.6)	22 (19.0)
LST-G-H	22 (6.5)	5 (4.3)
LST-G-M	176 (51.8)	86 (74.1)
Accompanied by large nodules			91.969	< 0.001
No	316 (92.9)	63 (54.3)
Yes	24 (7.1)	53 (45.7)
Accompanied by other adenomas			0.003	0.959
No	77 (22.6)	26 (22.4)
Yes	263 (77.4)	116 (77.6)

LST: Lateral developing tumors.

Table 3 Multivariate logistic regression analysis of risk factors for malignant transformation of colorectal lateral developing tumors.

Project	β value	Wald	OR (95%CI)	P value
Gender
Male			1
Female	-0.303	1.172	0.738 (0.426-1.279)	0.279
Lesion size
≤ 2 cm			1
> 2 cm	1.232	8.182	3.427 (1.474-7.968)	0.004
Location of lesion
Transverse colon			1
Cecum	-1.224	3.583	0.294 (0.083-1.044)	0.058
Ascending colon	0.573	1.866	1.773 (0.780-4.032)	0.172
Descending colon	0.380	0.369	1.463 (0.429-4.984)	0.543
Sigmoid colon	0.846	2.729	2.329 (0.854-6.352)	0.099
Rectum	0.930	4.849	2.534 (1.108-5.799)	0.028
Accompanied by large nodules
No			1
Yes	1.943	30.551	6.979 (3.504-13.900)	< 0.001
Endoscopic classification
LST-NG-F			1
LST-NG-PD	3.053	21.075	21.186 (5.864-76.544)	< 0.001
LST-G-H	2.204	7.555	9.064 (1.882-43.650)	0.006
LST-G-M	1.627	6.447	5.086 (1.449-17.852)	0.011

LST: Lateral developing tumors.

Univariate logistic regression analysis

Low-grade intraepithelial neoplasia, high-grade intraepithelial neoplasia and intramucosal carcinoma were included in the nonsubmucosal infiltration group, and submucosal invasive carcinoma was included in the submucosal infiltration group (0 = nonsubmucosal infiltration group, 1 = submucosal infiltration group). The results of univariate logistic regression analysis revealed that the location of the lesion, endoscopic classification and macronodules were relevant factors for submucosal infiltration (P < 0.05). Statistically significant variables in the univariate analysis (and adjusted for confounders) were selected for the multivariate unconditional logistic regression model, and independent variables were screened via the entry method. The results revealed that endoscopic typing (LST-NG-PD) and macronodules were independent risk factors for submucosal infiltration (all P < 0.05), as shown in Tables 4 and 5.

Table 4 Univariate logistic regression analysis of risk factors for submucosal infiltration in lateral developmental colorectal tumors, n (%).

Project	Non submucosal infiltration group (n = 422)	Submucosal infiltration group (n = 34)	χ2	P value
Gender,			2.952	0.086
Male	221 (52.4)	23 (67.6)
Female	201 (47.6)	11 (32.4)
Age			0.240	0.624
≤ 64	217 (51.4)	16 (47.1)
> 64	205 (48.6)	18 (52.9)
Disease size			3.465	0.063
≤ 2 cm	255 (60.4)	15 (44.1)
> 2 cm	167 (39.6)	19 (55.9)
Location of lesion			14.281	0.014
Cecum	54 (12.8)	0 (0.0)
Ascending colon	104 (24.6)	8 (23.5)
Transverse colon	104 (24.6)	5 (14.7)
Descending colon	24 (5.7)	2 (5.9)
Sigmoid colon	35 (8.3)	5 (14.7)
Rectum	101 (23.9)	14 (41.2)
Endoscopic classification			17.584	0.001
LST-NG-F	108 (25.6)	1 (2.9)
LST-NG-PD	48 (11.4)	10 (29.4)
LST-G-H	26 (6.2)	1 (2.9)
LST-G-M	240 (56.9)	22 (64.7)
Accompanied by large nodules			52.724	< 0.001
No	366 (86.7)	13 (38.2)
Yes	56 (13.3)	21 (61.8)
Accompanied by other polyps			0.513	0.474
No	97 (23.0)	6 (17.6)
Yes	325 (77.0)	28 (82.4)

LST: Lateral developing tumors.

Table 5 Multivariate logistic regression analysis of risk factors for submucosal infiltration in colorectal lateral developing tumors.

Project	β value	Wald	OR value (95%CI)	P value
Location of lesion
Transverse colon			1
Cecum	-18.416	0.000	0	0.997
Ascending colon	0.799	1.462	2.224 (0.593-3.697)	0.227
Descending colon	0.213	0.051	1.237 (0.387-5.797)	0.821
Sigmoid colon	0.846	1.250	2.330 (0.662-6.322)	0.264
Rectum	-0.420	0.350	0.657 (0.163-2.642)	0.554
Accompanied by large nodules
No			1
Yes	4.643	18.197	103.873 (12.303-877.016)	< 0.001
Endoscopic classification
LST-NG-F			1
LST-NG-PD	3.146	8.640	23.234 (2.837-64.408)	0.003
LST-G-H	1.750	1.441	5.756 (1.304-49.870)	0.230
LST-G-M	-0.594	0.174	0.552 (0.034-8.991)	0.676

LST: Lateral developing tumors.

DISCUSSION

The detection rate of colorectal LSTs in colonoscopy is 1.3% to 4.5%, accounting for 3% to 5% of the total polyps found by colonoscopy and accounting for 5.8% of early colorectal cancer cases[21-23]. LSTs have unique pathological features and development patterns and have greater malignant transformation potential than adenomatous polyps do[24]. In recent years, health awareness has gradually increased, colonoscopy screening has gradually become popular, and an increasing number of LSTs have been diagnosed and treated via endoscopy[25-27]. Because LST is closely related to colorectal cancer, early diagnosis and treatment are highly important for improving the survival period and quality of life of patients. The main treatment options for LST are traditional surgery and endoscopic therapy[28-30]. With the development of endoscopic equipment and instruments and improvements in endoscopic diagnosis and treatment technology, an increasing number of doctors are able to complete endoscopic EMR and ESD therapy, and endoscopic therapy has gradually become popular to avoid surgical trauma[31]. The selection of treatment for LST should be based on the size, nature and depth of invasion of the lesion, so a full understanding of the endoscopic and pathological characteristics of LST is highly important for the selection of appropriate treatment. For this purpose, we conducted this study to summarize and analyze the endoscopic and pathological features of colorectal LSTs, explore the risk factors for carcinogenic transformation and submucosal infiltration, and provide guidance for selecting the most appropriate treatment plan[32].

In this study, the sex ratio of patients was roughly the same, with slightly more males, whereas the literature reported that both males and females were more common in LST patients. The patients were 63.45 ± 9.23 years old (27-87 years old), indicating that colorectal LSTs were more common in middle-aged and older patients, which was consistent with previous findings. The results of this study revealed that sex and age were not risk factors for LST carcinogenesis or submucosal infiltration.

Colorectal LSTs grow laterally along the intestinal wall, and the height and color of the lesion are not significantly different from those of the surrounding normal mucosa; thus, it is easy to miss the diagnosis via colonoscopy[33-35]. In this study, the incidence of LSTs was high in the rectum and right half of the colon, suggesting that during colonoscopy, endoscopists should observe more carefully whether there are flat lateral growth lesions in the cecum, ascending colon, transverse colon, or rectum. LST-NG is mostly located in the ascending and transverse colon, and the intestinal preparation of the right colon is usually worse than that of the left colon. The colonic fold is high, and it is difficult to observe behind the fold, which easily results in a missed diagnosis of LST-NG[36]. Therefore, good intestinal preparation should be performed before colonoscopy, the doctor should patiently rinse and observe the location of inadequate intestinal preparation during the examination, and the endoscope can be reversed in the ascending colon. Improving the detection rate of the LST. LST-G-H is located mostly in the ileocecal part and transverse colon, and special attention should be given to the occlusion position of the ileocecal flap in the cecum. LST-G-M is mostly located in the rectum, and it is difficult to observe the occlusion position of the proximal anal margin of the rectum and the proximal Houston valve; thus, the endoscope should be reversed in the rectum to reduce the missed diagnosis rate. When the lesions are not clearly displayed, electronic and chemical staining of the endoscope can be used to display the lesions more clearly. In addition, our study revealed that more than three-quarters of patients with LST had other adenomatous polyps on examination, and the actual probability may be greater, suggesting that endoscopists should carefully screen for other adenomatous polyps when discovering LST lesions[37-39]. For high-risk lesions, particularly rectal LST-NG-PD > 2 cm, we recommend pre-resection endoscopic ultrasonography (EUS) to assess invasion depth and guide treatment planning. EUS can identify deep submucosal invasion (SM2-SM3) that may require surgical resection rather than endoscopic treatment. In our experience, 3 cases were converted to surgical management based on EUS findings suggesting deep invasion. Additionally, pelvic MRI may provide valuable information for large rectal lesions approaching the dentate line, helping assess proximity to critical structures. LST-NG and LST-G grew mainly in the horizontal direction but presented different histopathological characteristics. Large LST-NG has greater malignant potential and a greater risk of submucosal infiltration[40]. Compared with small polyps, LSTs > 2 cm had a much greater risk of developing submucosal invasive cancer (approximately 8%). LST-G-M evolved from LST-G-H, and the risk of submucosal infiltration increased to 10%. This study revealed that the cancer rates and submucosal infiltration rates of the four endoscope types were consistent, and the order from high to low was LST-NG-PD, LST-G-M, LST-G-H, and LST-NG-F. Compared with LST-G, LST-NG had a greater incidence of submucosal invasion despite a smaller tumor diameter, which was consistent with the findings of previous studies[41-43].

Our findings demonstrate that lesion size > 2 cm is an independent risk factor for carcinogenesis, which has important implications for treatment selection. For lesions > 2 cm, ESD achieved higher en-bloc resection rates (99.6%) compared to EMR (95.8%) and EMR-P (97.3%), though the difference was statistically significant (P < 0.05). The mean lesion diameter treated by ESD was significantly larger (3.17 ± 1.83 cm) than EMR (1.31 ± 0.36 cm) and EMR-P (1.65 ± 0.50 cm), reflecting appropriate case selection. While ESD requires longer operative time (73.40 ± 57.17 minutes vs 8.97 ± 9.04 minutes for EMR), it enables complete resection of large lesions with complex morphology, particularly LST-NG-PD and LST-G-M subtypes with large nodules. Given that these features are independent risk factors for submucosal invasion, ESD should be considered the preferred approach for LSTs > 2 cm, especially those with high-risk endoscopic features. Colorectal LSTs have relatively high incidence rates and cancer rates, and there is a certain risk of submucosal infiltration[44]. Therefore, analyzing the endoscopic characteristics of LSTs is highly important for accurately evaluating the pathological type and infiltration depth of colorectal LSTs before surgery for the selection of treatment. In this study, lesion size (> 2 cm), lesion location (rectum), endoscopic classification (LST-NG-PD, LST-G-H, and LST-G-M), and the presence of large nodules were independent risk factors for carcinogenesis. Endoscopic classification (LST-NG-PD) with macronodules (present) was an independent risk factor for submucosal infiltration. Owing to the lateral development and growth of the LST, the lesion boundary may not be clear. Therefore, in the process of colonoscopy, in addition to the location of the lesion, the size of the lesion (that is, the boundary) should also be defined. On the basis of careful observation with white light, endoscopic electronic and chemical staining can be used to visualize these findings more clearly. Nongranular lesions should be carefully observed for depression, and granular lesions should be noted for large nodules. Magnifying endoscopy can also be used to observe the microvessels and microstructures on the surface of the lesions in NBI mode. Types 2B and 3, which present as disorders or the disappearance of microvessels and microstructures, correspond to intramucosal carcinoma and submucosal invasive carcinoma, respectively, according to JNET typing. Compared with proximal colon LSTs, rectal LSTs are associated with a greater risk of cancer. Fortunately, rectal endoscopy is less difficult and has a lower risk of complications than proximal colon endoscopy because of its proximity to the anal margin and thicker intestinal wall[45].

In terms of pathology, in this study, the pathological results of 7 patients after endoscopic surgery indicated that the depth of invasion of the cancer had reached SM 2, the remaining patients underwent endoscopic curative resection, and no recurrence was found during follow-up. Among the 7 patients with deep SM2 infiltration, 1 had no evidence of recurrence or metastasis thus far, and the other 6 underwent additional surgery. No cancer cells were found at the broken end or in the lymph nodes dissected after surgery. Although surgery may be overtreated in these six patients, the current consensus is that the depth of invasion of the cancer reaches SM2, and in principle, additional surgery is needed. More follow-up studies are needed to verify whether the criteria for endoscopic curative resection should be further expanded upon in the future.

Limitations of this study. First, this was a single-center retrospective study. At the stage of research design, the relatively single object selected may distort the research results and cause selection bias. Therefore, selection bias related to the study design should be considered before the interpretation of the study results, and the accuracy of the results should be further ensured by correcting for confounding factors during the statistical analysis stage. Second, owing to the inherent defects of retrospective studies, some follow-up data and observation parameters are missing.

CONCLUSION

In summary, there are significant differences in the endoscopic and pathological characteristics of the four subtypes of LST. Lesion size (> 2 cm), location (rectum), endoscopic classification (LST-NG-PD, LST-G-H, and LST-G-M), and the presence of large nodules were independent risk factors for carcinogenesis. Endoscopic classification (LST-NG-PD) with macronodules (present) was an independent risk factor for submucosal infiltration. Endoscopic treatment of LST has fewer complications, is safe and effective, and different endoscopic treatment methods have their own advantages.