Kim KH, Myung E, Oh HH, Im CM, Seo YE, Kim JS, Lim CJ, You GR, Cho SB, Lee WS, Noh MG, Lee KH, Joo YE. Clinical and endoscopic characteristics of colorectal traditional serrated adenomas with dysplasia/adenocarcinoma in a Korean population. World J Gastrointest Oncol 2025; 17(2): 101780 [DOI: 10.4251/wjgo.v17.i2.101780]
Corresponding Author of This Article
Young-Eun Joo, MD, PhD, Professor, Department of Internal Medicine, Chonnam National University Medical School, No. 264 Seoyang Road, Hwasun-eup 58128, South Korea. yejoo@chonnam.ac.kr
Research Domain of This Article
Gastroenterology & Hepatology
Article-Type of This Article
Retrospective Study
Open-Access Policy of This Article
This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Ki-Hyun Kim, Eun Myung, Hyung Hoon Oh, Chan-Muk Im, Young-Eun Seo, Je-Seong Kim, Chae-June Lim, Ga-Ram You, Sung-Bum Cho, Wan-Sik Lee, Young-Eun Joo, Department of Internal Medicine, Chonnam National University Medical School, Hwasun-eup 58128, South Korea
Myung-Giun Noh, Kyung-Hwa Lee, Department of Pathology, Chonnam National University Medical School, Hwasun-eup 58128, South Korea
Author contributions: Kim KH and Myung E wrote the main text, they contributed equally as co-first author; Kim KH, Myung E, and Joo YE generated the idea and performed the computations; Oh HH, Im CM, Seo YE, Kim JS, Lim CJ, and You GR collected and analyzed the data; Oh HH, Im CM, and Kim KH collected the endoscopic images; Noh MG and Lee KH collected the pathological images; Cho SB, Lee WS, and Joo YE reviewed the analyzed statistical results; Joo YE supervised all processes; and all authors discussed the results and contributed to the final manuscript.
Supported by The First Research in Lifetime Grant from Chonnam National University Hospital Biomedical Research Institute, No. HCRI23005.
Institutional review board statement: The study was performed in accordance with the ethical principles of the Declaration of Helsinki and was approved by the Institutional Review Board of Chonnam National University Hwasun Hospital (No. CNUHH-2024-181).
Informed consent statement: All study participants, or their legal guardian, provided informed written consent prior to study enrollment.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Data sharing statement: The datasets used and/or analysed during the current study available from the first or corresponding author on reasonable request.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Young-Eun Joo, MD, PhD, Professor, Department of Internal Medicine, Chonnam National University Medical School, No. 264 Seoyang Road, Hwasun-eup 58128, South Korea. yejoo@chonnam.ac.kr
Received: September 26, 2024 Revised: October 28, 2024 Accepted: November 29, 2024 Published online: February 15, 2025 Processing time: 114 Days and 4.2 Hours
Abstract
BACKGROUND
Traditional serrated adenoma (TSA) is a rare and precancerous lesion of colorectal cancer. The clinical and endoscopic differentiations between TSAs without dysplasia or adenocarcinoma (TSAOs) and TSAs with dysplasia or adenocarcinoma (TSADs) remain unclear.
AIM
To evaluate the characteristics of colorectal TSAs and compare the characteristics of TSAOs with those of TSADs.
METHODS
This retrospective study included 193 patients who underwent endoscopic resection and received a pathologic diagnosis of TSA. We reviewed the medical, endoscopic, and histopathologic records of patients who underwent endoscopic resection of TSAs between January 2010 and December 2023.
RESULTS
TSAs were more frequently located in the rectosigmoid colon. Most TSAs had 0-Ip, 0-Isp, or 0-Is morphologies. The TSAD lesions were larger than TSAO lesions. TSAD lesions more commonly had a red color and an irregular border than TSAO lesions. TSAOs were usually treated using conventional endoscopic mucosal resection, whereas TSADs were treated using conventional endoscopic mucosal resection, endoscopic submucosal dissection, and surgery. Post-polypectomy bleeding was more common with TSADs than with TSAOs. Univariate analysis showed that gastrointestinal bleeding, red color, 0-IIa, irregular border, and lobular mucosal surface were significantly associated with TSADs. Multivariate analysis showed that gastrointestinal bleeding, an irregular border, and a lobular mucosal surface were significantly associated with TSADs.
CONCLUSION
TSAs with gastrointestinal bleeding, an irregular border, and a lobular mucosal surface are associated with an increased risk of dysplasia or adenocarcinoma.
Core Tip: Traditional serrated adenoma (TSA) is recognized as a precancerous lesion. However, the endoscopic features associated with the presence or absence of dysplasia or adenocarcinoma have not yet been clearly defined. In our study, we analyzed the medical records of 193 patients diagnosed with TSAs following endoscopic resection at Chonnam National University Hwasun Hospital. In our study, TSAs with dysplasia or adenocarcinoma was associated with gastrointestinal bleeding, an irregular border, and a lobular mucosal surface. These findings are expected to serve as important factors in determining the treatment strategy for the lesions.
Citation: Kim KH, Myung E, Oh HH, Im CM, Seo YE, Kim JS, Lim CJ, You GR, Cho SB, Lee WS, Noh MG, Lee KH, Joo YE. Clinical and endoscopic characteristics of colorectal traditional serrated adenomas with dysplasia/adenocarcinoma in a Korean population. World J Gastrointest Oncol 2025; 17(2): 101780
Colorectal cancer (CRC) is one of the most frequently diagnosed cancers and a leading cause of cancer-related morbidity and mortality in the world[1]. CRC develops from the accumulation of multiple genetic and epigenetic alterations in the normal colorectal epithelium. Approximately 70% of sporadic CRCs develop via the adenoma-carcinoma sequence pathway, which leads to the transformation of the normal colorectal epithelium to conventional adenomatous polyps, low-grade to high-grade dysplasia, and finally carcinoma[2,3]. Recent reports suggest that colorectal serrated lesions with characteristic sawtooth-like in-folding of the epithelial crypts lead to the development of CRC via the serrated neoplasia pathway that progresses by methylating tumor suppressor genes. The serrated neoplasia pathway has increasingly been recognized as an important alternative pathway accounting for up to 30% of sporadic CRC[4-8]. Colorectal serrated lesions were classified into the following 4 categories in 2019 by the World Health Organization: Hyperplastic polyps (HPs), sessile serrated lesions (SSLs), traditional serrated adenomas (TSAs), and unclassified serrated adenomas. HPs account for approximately 75% of all diagnosed serrated lesions but rarely progress to cancer. SSLs represent the second most diagnosed serrated lesions with a prevalence of 5%-10% in the general population. Of all serrated lesions, TSAs have a prevalence is < 1% in the general population undergoing screening colonoscopy. SSLs and TSAs are the precursor epithelial polyps that can develop into CRC[4-8]. Therefore, endoscopists should be aware of the clinical and endoscopic characteristics of SSLs and TSAs to ensure early detection, appropriate resection, and an optimal surveillance interval. In particular, if the precancerous lesion is accompanied by dysplasia or adenocarcinoma, complete resection should be performed to prevent recurrence and progression to cancer.
According to previously published studies, TSAs, similar to HPs, commonly occur in the left colon. TSAs are larger than SSLs and have a polypoid appearance, unlike SSLs. TSAs primarily affect patients aged > 50 years and prevalence does not differ by sex. Histologically, TSAs show elongated, narrow penicillate nuclei with dispersed chromatin and eosinophilic cytoplasm, ectopic crypt foci, and typical slit-like clefted serrations[9-13]. However, because of their rarity, the clinical and endoscopic features of TSAs have not yet been fully elucidated. In particular, comparison of clinical and endoscopic characteristics of TSAs without dysplasia or adenocarcinoma (TSAOs) and TSAs with dysplasia or adenocarcinoma (TSADs) is important for the development of future treatment options to prevent recurrence and progression of TSAs. Therefore, this study focused on assessing the clinical and endoscopic features of TSAs and compare the features between TSAOs with TSADs.
MATERIALS AND METHODS
Study design and population
This retrospective study assessed consecutive patients with endoscopically resected lesions pathologically diagnosed as TSAO and TSAD at Chonnam National University Hwasun Hospital, Jeonnam, Korea, between January 2010 and December 2023. A total of 193 TSA lesions were retrospectively analyzed for various clinicopathological characteristics by reviewing medical, endoscopic, and histopathologic records of enrolled patients. The study was performed in accordance with the ethical principles of the Declaration of Helsinki and was approved by the Institutional Review Board of Chonnam National University Hwasun Hospital (IRB No. CNUHH-2024-181).
Endoscopic examination and histologic analysis of TSAs
The patients were inspected with video colonoscopes (Olympus CF-240I, CF-H260, or CF-HQ290; Olympus, Tokyo, Japan). Three professional gastrointestinal endoscopists reviewed the endoscopic findings related to TSAs and assessed conventional white-light colonoscopy visuals. The endoscopic features were analyzed based on criteria validated by Mizuguchi et al[13], which included color assessments (white or red) (Figure 1A), border definitions (distinct or irregular) (Figure 1B), and mucosal surface characteristics (smooth or lobular) (Figure 1C). According to the Paris classification, superficial lesion morphology can be classified into three main categories: (1) Protruding (0-I); (2) Non-protruding and non-excavated (0-II); and (3) Excavated (0-III). Type 0-I lesions include sub-classifications of pedunculated (0-I), sessile (0-Is), or mixed (0-Isp) forms, while type 0-II lesions are categorized as slightly elevated (0-IIa), flat (0-IIb), or depressed (0-IIc). The histological analysis of TSAOs and TSADs was conducted separately by two gastrointestinal pathologists at our institution, following the 2019 World Health Organization criteria for features like villous and occasionally filiform architecture, eosinophilic cytoplasm, penicillate nuclei, ectopic crypts, undulant serration, and any clear demarcation with conventional adenoma-like regions. TSAs were categorized based on dysplastic changes as without dysplasia, low-grade dysplasia, high-grade dysplasia, or adenocarcinoma (Figure 2). In cases where histologic interpretations differed, the pathologists engaged in further discussions to reach an agreement.
Figure 1 White-light colonoscopy images of traditional serrated adenomas in a representative case.
A: Color - white or red; B: Border - distinct or irregular; C: Surface - smooth or lobular.
Figure 2 Histopathologic features observed with hematoxylin and eosin staining of the resected specimens of traditional serrated adenomas.
A: Traditional serrated adenomas (TSA) without dysplasia shows a saw-tooth appearance of the crypts with abundant eosinophilic cytoplasm and a basal/central elongated nucleus [hematoxylin and eosin (HE) staining, × 100]; B: TSA with low-grade dysplasia (HE staining, × 50); C: TSA with high-grade dysplasia (HE staining, × 100); D: TSA with adenocarcinoma (HE staining, × 50).
Statistical analysis
The clinical and endoscopic features of TSAOs and TSADs were analyzed through the χ² test, Student’s t-test, or analysis of variance, as appropriate. The data were summarized using proportions for categorical variables and mean values accompanied by SD for continuous variables. Furthermore, a binary logistic regression analysis was applied to determine the risk factors associated with TSADs. All statistical evaluations were performed with the Statistical Package for the Social Sciences (SPSS, version 26.0; SPSS Inc., Chicago, IL, United States). A P value of less than 0.05 was deemed statistically significant.
RESULTS
Baseline characteristics of TSA patients
The baseline characteristics of TSA patients are summarized in Table 1. The mean age of enrolled patients was 63.2 ± 13.8 years (range: 18.0-89.0 years). The study patients group included 93 male (48.2%) and 100 female (51.8%). The mean body mass index was 23.9 ± 3.4 kg/m2 (range: 17.4-37.7 kg/m2). A history of alcohol consumption and smoking was noted in 104 (53.9%) and 59 (30.6%) patients, respectively. Hypertension, diabetes mellitus, and dyslipidemia were noted in 81 (42.0%), 40 (20.7%), and 31 (16.1%) patients, respectively. A total of 49 (25.4%) patients received anti-thrombotic medications, including aspirin, warfarin, or new oral anticoagulants. Of the total, 25 patients (12.9%) showed gastrointestinal symptoms including bleeding and obstruction. The mean size of TSAs was 18.1 ± 13.5 mm (range: 3.0-70.0 mm). Of the 193 detected TSA lesions, 134 lesions (69.4%) were localized in the rectosigmoid colon. The most common location was the rectum (74, 38.3%), followed by the sigmoid colon (60, 31.1%), ascending colon (27, 14.0%), transverse colon (20, 10.4%), descending colon (9, 4.7%), and cecum (3, 1.6%). The lesions were most commonly white (82, 42.5%) and red (111, 57.5%). Based on the Paris classification (32), the numbers of patients categorized as 0-Ip and 0-Isp, 0-Is, 0-IIa, and 0-IIa + IIc were 85 (44.1%), 67 (34.7%), 34 (17.6%), and 7 (3.6%), respectively. With regard to endoscopic features, 164 (85.0%) had a distinct border, whereas 29 (15.0%) had an irregular border, and 89 (46.1%) had a mucosal surface, whereas 104 (53.9%) had a lobular mucosal surface. According to histologic examination, 122 (63.2%) lesions were TSAOs, and 71 (36.8%) lesions were TSADs [low-grade dysplasia, 51 (26.4%); high-grade dysplasia, 14 (7.3%); adenocarcinoma, 6 (3.1%)]. With regard to the prevalence of synchronous colorectal neoplasms in patients with TSA, 62 (32.1%) had conventional adenoma with low-grade dysplasia, 17 (8.8%) had HP, 13 (6.7%) had conventional adenoma with high-grade dysplasia and colorectal adenocarcinoma, and 2 (1.0%) had SSLs. TSAs were resected using polypectomy such as cold biopsy (1, 0.5%), cold endoscopic mucosal resection (EMR) (6, 3.1%), conventional EMR (121, 62.7%), endoscopic submucosal dissection (ESD) (52, 26.9%), or surgery (11, 5.7%). The post-procedure bleeding rate was 47.7% (92/193) and the perforation rate was 0.5% (1/193) (Table 1).
Table 1 Baseline characteristics of patients with traditional serrated adenomas, n = 193.
Variables
n (%)
Patient-related factors
Age (years), mean ± SD (range)
63.2 ± 13.8 (18.0-89.0)
Sex
Male
93 (48.2)
Female
100 (51.8)
BMI (kg/m2), mean ± SD (range)
23.9 ± 3.4 (17.4-37.7)
Obesity
Underweight (< 18.5)
6 (3.1)
Normal (18.5 ≤ n < 23.0)
76 (39.4)
Overweight (23.0 ≤ n < 25.0)
45 (23.3)
Obesity (≥ 25.0)
66 (34.2)
Alcohol
None
89 (46.1)
Quit
51 (26.4)
Current
53 (27.5)
Smoking
None
134 (69.4)
Quit
34 (17.6)
Current
25 (13.0)
Hypertension
81 (42.0)
Diabetes mellitus
40 (20.7)
Dyslipidemia
31 (16.1)
Anti-platelet agent (n = 49, 25.4%)
Aspirin
32 (16.6)
Warfarin/NOAC
5 (2.6)
Dual anti-platelet agent
12 (6.2)
History of colorectal cancer
27 (14.0)
Symptom
None
168 (87.0)
Gastrointestinal bleeding
24 (12.4)
Obstruction
1 (0.5)
Lesion-related factors
Size (mm), mean ± SD (range)
18.1 ± 13.5 (3.0-70.0)
Diminutive (1-5 mm)
16 (8.3)
Small (6-9 mm)
46 (23.8)
Large (> 10 mm)
131 (67.9)
Location
Cecum
3 (1.6)
Ascending colon
27 (14)
Transverse colon
20 (10.4)
Descending colon
9 (4.7)
Sigmoid colon
60 (31.1)
Rectum
74 (38.3)
Color
White
82 (42.5)
Red
111 (57.5)
Morphology (Paris classification)
0-Ip, 0-Isp
85 (44.1)
0-Is
67 (34.7)
0-IIa
34 (17.6)
0-IIa + IIc
7 (3.6)
Border
Distinct
164 (85.0)
Irregular
29 (15.0)
Mucosal surface
Smooth
89 (46.1)
Lobular
104 (53.9)
Dysplasia (n = 71, 36.8%)
LGD
51 (26.4)
HGD
14 (7.3)
ADC
6 (3.1)
Associated lesion (n = 104, 53.9%)
Hyperplastic polyp
17 (8.8)
Sessile serrated lesion
2 (1.0)
Traditional serrated adenoma
10 (5.2)
Conventional adenoma with LGD
62 (32.1)
Conventional adenoma with HGD/ADC
13 (6.7)
Procedure-related factors
Removal methods
Cold biopsy
1 (0.5)
Cold snare EMR
6 (3.1)
Conventional EMR
121 (62.7)
ESD
52 (26.9)
Operation
11 (5.7)
Observation
2 (1.0)
Post-procedural complications (n = 93, 48.2%)
Bleeding
92 (47.7)
Perforation
1 (0.8)
Treatment methods of complications
APC
18 (9.3)
Coagrasper
35 (18.1)
Hemoclipping
40 (20.7)
Comparison of clinical characteristics of TSAOs and TSADs
The cohort of TSAs consisted of 122 TSAOs and 71 TSADs. Regarding patient-related factors, no statistically significant differences were observed between the TSAO and TSAD groups in terms of age, sex, body mass index, prevalence of obesity, alcohol, smoking, hypertension, diabetes mellitus, dyslipidemia, use of anti-thrombotic, gastrointestinal symptoms, and history of CRC. With regard to lesion-related factors, the mean tumor size was significantly higher in TSADs than in TSAOs (P = 0.003). The 0-Is lesions occurred more frequently in the TSAD group, whereas 0-IIa lesions occurred more frequently in the TSAO group (P = 0.005). Analysis of endoscopic features showed that a red lesion, an irregular border, and a lobular mucosal surface were more commonly associated with TSADs than with TSAOs (P = 0.001 and < 0.001, respectively). Non-neoplastic lesions such as HPs and neoplastic lesions such as SSL, TSA, and conventional adenomas with low-grade dysplasia and high-grade dysplasia/adenocarcinoma were more commonly detected in the TSAD group than in the TSAO group (P < 0.001). No statistically significant differences were observed in location, morphology, and mucosal surface between the TSAO and TSAD groups. With regard to procedural factors, conventional EMR, ESD, and surgery were more commonly performed in the TSAD group, whereas conventional EMR was more frequently performed in the TSAO group (P < 0.001). Additionally, post-procedural bleeding was more frequently reported in TSADs compared to TSAOs (P < 0.001), and hemoclipping for hemostasis was performed more often in the TSAD group (P < 0.001) (Table 2).
Table 2 Comparison of clinical characteristics between traditional serrated adenomas without and with dysplasia or adenocarcinoma, n (%).
Variables
TSAOs (n = 122)
TSADs (n = 71)
P value
Age (years), mean ± SD (range)
61.1 ± 14.5 (18.0-84.0)
66.7 ± 11.8 (36.0-85.1)
0.072
Sex
0.234
Male
63 (51.6)
30 (42.3)
Female
59 (48.4)
41 (57.7)
BMI (n = 499), mean ± SD (range)
24.1 ± 3.7 (17.4-37.7)
23.7 ± 2.9 (17.7-30.6)
0.128
Obesity
0.726
Underweight (< 18.5)
3 (2.5)
3 (4.2)
Normal (18.5-23.0)
46 (37.7)
30 (42.3)
Overweight (23.0-25.0)
31 (25.4)
14 (19.7)
Obesity (≥ 25.0)
42 (34.4)
24 (33.8)
Alcohol
0.177
None
52 (42.6)
37 (52.1)
Quit
31 (25.4)
20 (28.2)
Current
39 (32.0)
14 (19.7)
Smoking
0.681
None
82 (67.2)
52 (73.2)
Quit
23 (18.9)
11 (15.5)
Current
17 (13.9)
8 (11.3)
Hypertension
45 (36.9)
36 (50.7)
0.061
Diabetes mellitus
29 (23.8)
11 (15.5)
0.171
Dyslipidemia
21 (17.2)
10 (14.1)
0.568
Anti-platelet agent (n = 49)
0.521
Aspirin
23 (18.9)
9 (12.7)
Warfarin/NOAC
3 (2.5)
2 (2.8)
Dual anti-platelet agent
9 (7.4)
3 (4.2)
History of colorectal cancer
16 (13.1)
11 (15.5)
0.671
Symptom
0.051
None
111 (91.0)
57 (80.3)
Gastrointestinal bleeding
10 (8.2)
14 (19.7)
Obstruction
1 (0.8)
0 (0.0)
Lesion-related factors
Size (mm), mean ± SD (range)
12.7 ± 8.0 (3.0-55.0)
27.3 ± 15.9 (5.0-70.0)
0.003
Diminutive (1-5 mm)
16 (13.1)
0 (0.0)
Small (6-9 mm)
31 (25.4)
15 (21.1)
Large (> 10 mm)
75 (61.5)
56 (78.9)
Location
0.177
Cecum
1 (0.8)
2 (2.8)
Ascending colon
13 (10.7)
14 (19.7)
Transverse colon
12 (9.8)
8 (11.3)
Descending colon
8 (6.6)
1 (1.4)
Sigmoid colon
42 (34.4)
18 (25.4)
Rectum
46 (37.7)
28 (39.4)
Color
0.001
White
63 (51.6)
19 (26.8)
Red
59 (48.4)
52 (73.2)
Morphology (Paris classification)
0.005
0-Ip, 0-Isp
53 (43.4)
32 (45.1)
0-Is
35 (28.7)
32 (45.1)
0-IIa
30 (24.6)
4 (5.6)
0-IIa + IIc
4 (3.3)
3 (4.2)
Border
< 0.001
Distinct
114 (93.4)
50 (70.4)
Irregular
8 (6.6)
21 (29.6)
Mucosal surface
0.058
Smooth
62 (50.8)
27 (38.0)
Lobular
60 (49.2)
44 (62.0)
Associated lesion (n = 104, 53.9%)
Non-neoplastic lesions (n = 17, 8.8%)
5 (4.2)
12 (16.2)
< 0.001
Hyperplastic polyp
5 (4.2)
12 (16.2)
Neoplastic lesions (n = 87, 45.1%)
48 (40.3)
39 (52.7)
< 0.001
Sessile serrated lesion
1 (0.8)
1 (1.4)
Traditional serrated adenoma
3 (2.5)
7 (9.5)
Conventional adenoma with LGD
37 (31.1)
25 (33.8)
Conventional adenoma with HGD/ADC
7 (5.9)
6 (8.1)
Procedure-related factors
Removal methods
< 0.001
Cold biopsy
1 (0.8)
0 (0.0)
Cold EMR
6 (4.9)
0 (0.0)
Conventional EMR
97 (79.5)
24 (44.4)
ESD
13 (10.7)
22 (40.7)
Operation
3 (2.5)
8 (14.8)
Observation
2 (1.6)
0 (0.0)
Post-procedural complications (n = 93, 48.2%)
< 0.001
Bleeding
44 (36.1)
48 (67.6)
Perforation
1 (0.8)
0 (0.0)
Treatment method of complication
< 0.001
APC
15 (12.3)
3 (4.2)
Coagrasper
17 (13.9)
18 (25.4)
Hemoclipping
13 (10.7)
27 (38.0)
Univariate analysis of risk factors associated with TSADs
The univariate analysis results examining risk factors related to TSADs are summarized in Table 3. For patient-related factors, no significant associations were identified between dysplasia risk and variables such as gender or obesity. The proportion of patients experiencing gastrointestinal bleeding was significantly higher in the TSAD group than in the TSAO group [odds ratio (OR) = 2.726; 95% confidence interval (CI): 1.140-6.521; P = 0.024]. With regard to lesion-related factors, a red-colored lesion was positively associated with the risk of dysplasia (OR = 9.182; 95%CI: 4.062-20.759; P < 0.001) compared to a white-colored border. Based on the Paris classification of endoscopic morphology, there was a higher risk of dysplasia with the 0-IIa morphology (OR = 0.221; 95%CI: 0.071-0.685; P = 0.009) than with the 0-Ip and 0-Isp morphologies. The analysis of endoscopic features showed that an irregular border was positively associated with the risk of dysplasia (OR = 5.985; 95%CI: 2.484-14.423; P < 0.001) (Table 3).
Table 3 Univariate logistic regression analysis of risk factors associated with traditional serrated adenomas with dysplasia or adenocarcinoma.
Variables
Odds ratio
95% confidence interval
P value
Sex
Male
0.685
0.380-1.236
0.209
Female
1.0
Obesity
Normal (18.5-23.0)
1.0
Underweight (< 18.5)
1.533
0.290-8.105
0.615
Overweight (23.0-25.0)
0.692
0.317-1.512
0.356
Obesity (≥ 25.0)
0.876
0.444-1.730
0.703
Symptom
Gastrointestinal bleeding
2.726
1.140-6.521
0.024
Color
White
1.0
Red
3.209
1.735-5.934
< 0.001
Morphology (Paris classification)
0-Ip, 0-Isp
1.0
0-Is
1.514
0.791-2.900
0.211
0-IIa
0.221
0.071-0.685
0.009
0-IIa + IIc
1.242
0.261-5.911
0.785
Border
Distinct
1.0
Irregular
5.985
2.484-14.423
< 0.001
Mucosal surface
Smooth
1.0
Lobular
1.684
0.928-3.057
0.087
Multivariate analysis of TSADs risk factors
The results of the multivariate analysis identifying risk factors associated with TSADs are summarized in Table 4. Multivariate logistic regression analysis showed that TSADs with gastrointestinal bleeding (OR = 2.726; 95%CI: 1.022-7.824; P = 0.045), an irregular border (OR = 8.238; 95%CI: 2.606-26.040; P < 0.001), and lobular mucosal surface (OR = 2.529; 95%CI: 1.140-5.611; P = 0.022) are significantly associated with the risk of dysplasia (Table 4).
Table 4 Multivariate logistic regression analysis of risk factors associated with traditional serrated adenoma with dysplasia or adenocarcinoma.
Variables
Odds ratio
95% confidence interval
P value
Symptom
Gastrointestinal bleeding
2.828
1.022-7.824
0.045
Color
White
1.0
Red
1.889
0.896-3.981
0.095
Morphology (Paris classification)
0-Ip, 0-Isp
1.0
0-Is
1.121
0.528-2.380
0.766
0-IIa
0.497
0.150-1.647
0.253
0-IIa + IIc
1.176
0.213-6.489
0.852
Border
Distinct
1.0
Irregular
7.314
2.508-21.333
< 0.001
Mucosal surface
Smooth
1.0
Lobular
2.424
1.147-5.125
0.020
DISCUSSION
TSAs are uncommon, serrated lesions that have a potential for malignant transformation[4-8]. However, owing to their rarity, research concerning the clinical and endoscopic features of TSAs and their association with the risk of dysplasia or adenocarcinoma is lacking. Therefore, we focused on the clinical and endoscopic characteristics based on the presence of dysplasia or adenocarcinoma in TSAs. TSAs commonly occur in patients aged > 50 years and have no significant predilection for either sex. TSAs are more commonly located in the distal colon. Endoscopically, they often present reddish, pedunculated or sessile lesions with pinecone-like or branch coral-shape and are usually > 5 mm in size[11-15]. In our study, the mean age of the enrolled patients was 63.2 years, and no significant differences were observed between sexes. Of the total, 74.1% of TSAs were localized in the rectosigmoid and descending colon, 57.5% had a red color, and 78.7% had pedunculated or sessile morphologies (0-Ip, 0-Isp, and 0-Is). The mean size of TSAs was 18.1 mm. Our observations for the location and morphology of TSAs are in line with those of other and our previous studies[16-20].
Previous studies have reported a cumulative CRC incidence of 1.34% in patients with TSA, which is similar to that in patients with conventional advanced adenoma, and 65.1% of patients with TSA were diagnosed with high-risk neoplasia at follow-up surveillance colonoscopy[17]. In TSAs, both conventional adenoma-like dysplasia and serrated dysplasia can be observed[19-22]. TSAs are hypothesized to acquire increasing degrees of cytological atypia before the development of CRC[10,23-25]. Therefore, endoscopists should be aware of the unique features of TSA, a precancerous lesion, to ensure their early detection and appropriate resection and an optimal surveillance interval. The differentiation between TSAOs and TSADs is clinically important. This distinction also has a significant effect on the choice of procedural methods for achieving complete removal of the lesions.
In our study, the mean tumor size was significantly higher in the TSAD than in the TSAO group. The analysis of endoscopic features showed that red color and an irregular border were more commonly found in the TSAD group than in the TSAO group. Lesions classified 0-Is were more frequently found in the TSAD group, whereas 0-IIa lesions were more frequently found in the TSAO group. Non-neoplastic and neoplastic precursor lesions were more commonly detected in the TSAD group than in the TSAO group. Previously, TSAs were larger in those with conventional epithelial dysplasia compared with those without. However, the gross morphology of TSAs did not differ according to the status of conventional epithelial dysplasia. Furthermore, contrary to our results, the frequency of synchronous precursor lesions was higher among TSAs with conventional epithelial dysplasia than in those without[11]. These differences in results could be attributed to the smaller sample size and the unavoidable selection bias in our study.
Although our results are inconsistent with those of previous studies, our study shows that the prevalence of neoplastic lesions is higher among TSADs than in TSAOs. Previous studies have associated the presence of SSLs with the presence of synchronous colorectal neoplastic lesions[26-28]. Furthermore, advanced adenomas featuring high-grade dysplasia and adenocarcinoma were observed to be more prevalent in SSLs with dysplasia compared to those without dysplasia[28]. Furthermore, a previous study showed a statistically significant higher risk of synchronous advanced neoplasms detected colonoscopically with TSAs than without[12]. Therefore, patients with TSAs, such as patients with SSLs, need meticulous endoscopic observation to detect synchronous neoplastic lesions.
In our study, ESD was more frequently performed in TSADs, whereas EMR was more frequently performed in TSAOs. Because TSADs were larger and more commonly had irregular borders than TSAOs in our study, use of ESD was more likely for complete endoscopic resection. Post-procedural bleeding occurred more frequently in TSADs than in TSAOs, which could be attributed to neoangiogenesis that occurs during the transition to dysplasia and adenocarcinoma[28,29]. However, it is anticipated that various factors such as size and treatment methods may be associated with post-procedural bleeding, so further research is needed. On univariate analysis, gastrointestinal bleeding, red color, 0-IIa type morphology, and an irregular border were significantly associated with TSAD development. Lobular mucosal surface showed a weak positive association with TSADs although the association was not statistically significant. On multivariate analysis, gastrointestinal bleeding, irregular border, and lobular mucosal surface were significantly associated with TSADs.
Previous studies on TSA are available. However, most of these studies are a part of broader analyses of serrated lesions, which primarily focus on SSLs due to their higher prevalence. Furthermore, research specifically limited to TSAs tends to emphasize immunohistochemical analysis rather than endoscopic features. These analytical aspects are not readily predictable or applicable by endoscopists during endoscopic procedures. Our study is valuable as it highlights the endoscopic characteristics based on the presence or absence of dysplasia in TSAs, which I believe provides direct assistance in determining and planning endoscopic treatment strategies. Our study has some limitations. First, this study is a retrospective study conducted at a single tertiary hospital in Korea. Second, the TSAO and TSAD groups had heterogeneous patient populations, which resulted in selection biases. Owing to these limitations, our findings may not be generalizable to the overall patient population. In future, large prospective, multicenter studies are needed to further validate of our findings.
CONCLUSION
TSAs exhibiting gastrointestinal bleeding, irregular borders, and lobular mucosal surfaces are associated with an increasing risk of dysplasia or adenocarcinoma. Consequently, these characteristics may serve as useful indicators for complete en bloc resection in immediate decision-making for the resection of TSAs.
Footnotes
Provenance and peer review: Unsolicited article; Externally peer reviewed.
Peer-review model: Single blind
Specialty type: Oncology
Country of origin: South Korea
Peer-review report’s classification
Scientific Quality: Grade B, Grade C
Novelty: Grade C, Grade C
Creativity or Innovation: Grade B, Grade C
Scientific Significance: Grade B, Grade C
P-Reviewer: Tsuji Y S-Editor: Wei YF L-Editor: A P-Editor: Zhang YL
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