Introduction

Endoscopic diagnosis and resection strategy of colorectal laterally spreading tumors (LSTs) is a relevant topic of debate. Current guidelines suggest that LSTs can be treated with endoscopic mucosal resection (EMR) provided that superficial submucosal invasion (SMI) stigmata are ruled out. By contrast, the treatment of choice for high risk SMI lesions should be en bloc resection with endoscopic submucosal dissection (ESD).

Aims & Methods

Since prediction of SMI risk is still challenging, in this study we evaluated which endoscopic features associated with presence of SMI in LSTs.
In this monocentric retrospective study, we included all patients with resected LSTs between January 2018 and November 2023. Lesions were classified according to morphology into granular (G), granular mixed (GM) and non granular (NG) phenotype. Paris Classification, Kudo pit Pattern, location and lesion diameter were evaluated as predictors of SMI. Univariate and multivariate logistic regression analysis was performed to assess predictors of SMI.

Results

Overall, 459 lesions were analyzed: n=172 NG-LST (37,5%), n=172 GM-LST (37,5%) and n=115 G-LST (25%). Superficial SMI was detected in 35 NG-LSTs (20,3%) , 21 GM-LSTs (12,2%) and 4 G-LSTs (3,5%). In the NG-LST group the prevalence of SMI was non-significantly higher in distal compared to proximal colon (24,5 % vs 17% , OR=1.59 [0.70-3.62] p= 0.27). According to Paris classification, the risk of SMI was significantly higher in depressed NG-LSTs (Paris IIc- IIa + IIc) compared to non-depressed lesions (31 % vs. 12%, OR=3.62 [1.59-8.26]; p=0.002).
In GM-LSTs cohort, a not significantly higher SMI prevalence was reported comparing distal with proximal lesions (12,5% vs 5,9%, OR=2,26 [0.61-8.30] p=0.22), whereas rectal lesions showed significant higher risk than proximal lesions (22,9% vs 5,9 %, OR=5.87 [1.94-17.73]; p= 0.002). Kudo pit pattern Vi lesions in comparison to Kudo pit pattern IIIs/IIIL/IV lesions showed a significantly higher SMI prevalence both in NG-LSTs (32% vs. 2%, OR=36.57 [4.80-278.60]; p< 0.001) and in GM-LSTs (73% vs 5%, OR=40.36 [11.96-136.18]; p <0.001). Besides, in GM-LST group a lesion diameter ≥4 cm was associated with higher SMI prevalence only in rectal lesions (40% vs 5%, OR 11.33 [1.33-96.81]; p=0.03).
At the multivariate analysis, independent predictors of SMI presence were Kudo pit pattern Vi (OR 35.02 [4.31-284.85] p<0,001) in NG-LSTs, and Kudo pit pattern Vi (OR 74.15 [14.08-390.43], p<0.001) and rectal lesions (OR 13.45 [2.00- 90.25], p=0,007) in GM-LSTs.

Conclusion

Our study confirmed that NG-LST lesions deliver a higher overall risk of SMI than GM-LSTs and G-LSTs, independently on the location. GM-LSTs carried an intermediate risk of SMI and, considering only rectal lesions, size was an important risk factor for SMI. Furthermore, the Kudo pit pattern was an independent risk factor for SMI in both groups. As a consequence, our study stresses that a proper optical diagnosis is paramount in order to stratify SMI risk and choose the appropriate treatment for these lesions.

Introduction

International guidelines recommend endoscopic submucosal dissection (ESD) for en-bloc resection of rectal lesions suspected of submucosal invasive cancer (SMI). ESD achieves favorable outcomes for benign lesions and early rectal cancers (ERC) with superficial (<1000μm) SMI. However, for ERCs with deep (≥1000μm) SMI, the rate of histologically radical (R0) resection remains suboptimal, at maximum 64% for SM2-3 lesions, even in expert centres. The muscle-retracting sign (MRS) has emerged as a potential endoscopic marker of deep SMI detected during endoscopic resection. Predicting deep SMI is particularly relevant in rectal lesions, as incorrect selection of resection modality may lead to non-radical endoscopic resections and the need for surgical salvage, which carries significant morbidity. To address some of these limitations, we applied the novel pocket-detection method (PDM) for MRS detection. This approach enhances visualization of the submucosal space and facilitates early identification of the MRS.

Aims & Methods

The aim of this study was to evaluate the diagnostic accuracy of the MRS detected using the PDM as an innovative approach for identifying deeply invasive ERC during endoscopic resection of rectal lesions.
In this prospective, observational, single-centre study consecutive rectal lesions that underwent endoscopic resection using the PDM between August 2023 and March 2025 were included. Directionality of initial submucosal dissection targeted any morphological or surface vascular pattern at risk of deep SMI to attempt MRS identification. Histopathology was the reference standard for MRS diagnostic accuracy in detecting deep SMI. Deep SMI was defined as ≥1000μm invasion from the muscularis mucosa at histopathology.

Results

38 rectal lesions, median size 30 mm (IQR 20-40), were included. PDM for MRS detection was successful in all cases, with MRS-positive in 15/38 (39.5%). Deep SMI was confirmed in 15/38 (39.5%). Accuracy of MRS-positive for deep SMI detection was 84.2%, (95% CI 69.6-92.6%), sensitivity 80% (95% CI 54.8-92.9%), specificity 87% (95% CI 67.9-95.5%), positive predictive value 80% (95% CI 54.8-92.9%), negative predictive value 87% (95% CI 67.9-95.5%), positive likelihood ratio 6.13, negative likelihood ratio 0.23, area under the curve 0.83 (95% CI: 0.71–0.96). The rate of R0 resection was 92.1% (35/38).

Conclusion

MRS detected using the PDM demonstrated moderate-to-high accuracy in predicting deep SMI in early rectal cancer. This finding may allow selection of endoscopic resection strategy based on invasion depth.

Introduction

Laterally spreading colorectal tumors (LSTs) are defined as ≥10 mm non polypoid lesions with lateral growth, representing between 1% and 6% of all colorectal lesions.
The clinical relevance of LSTs is strictly associated with the risk of covert (ie, without clear signs of invasion) submucosal invasive cancer (SMIC) due to its implications on both the endoscopic approach and the need of subsequent surgery.

Aims & Methods

According to European guidelines, Non-Granular Laterally Spreading Tumors (LSTNGs) require en-bloc resection due to the increased risk of covert submucosal Invasive cancer (SMIC). The overall reported SMIC of LST-NGs is 11.7 %, varying from near 5% for flat elevated (FE) to near 30% for pseudodepressed (PD) subtypes.
However, this risk stratification is mainly based on data from Asian cohorts, while Western data on LST-NGs management are heterogeneous and poor.
Thus, we aimed to evaluate risk stratification of SMIC in a Western cohort of LSTNGs according to endoscopical features.
All LST-NGs evaluated for resection in our academic tertiary referral centre from 2016 to 2022 and prospectively collected in a dedicated database (comprehending clinical, endoscopical and histological characteristics) were analysed. Univariate and multivariate analysis were conducted to assess predictors of covert SMIC.

Results

We included 197 LST-NGs, 149 (75.6%) FE and 48 (24.4%) PD. Mean age of patients (F: 39%) was 69.1±8.8 (yrs±SD). Mean lesions size was 22.4±8.6 (mm±SD).
The LSTs location was 149 (75.6%) in Right colon, 33 (16.8%) in Left colon and 15 (7.6%) in the Rectum. Vascular pattern was JNET 2A in 162 (82.2%), JNET 2B in 35 (17.8%), while pit pattern was invasive (Kudo Vi) in 30 (15.2%) and non-invasive (Kudo II-III) in 167 (84.8%).
SMIC was found in 22 (11.2%) of LST-NGs, 17 (77.3%) were PD and 5 (22.7%) were FE. Of these, 8 (36.4%) underwent surgery upfront and 14 (63.6%) were treated endoscopically, with an en-bloc resection in 85.7% of cases. Statistically significant predictive factors of SMIC were found to be: size >20 mm [OR (95%CI): 4.55 (1.62; 16.2)], Rectal location [OR (95%CI): 6.92 (2.09; 21.8)], PD subtype [OR (95%CI): 15.8 (5.77; 51.0)], Kudo Vi [OR (95%CI): 42.4 (14.4; 147)] and JNET 2B [OR (95%CI): 29.7 (10.4; 99.4)].
At multivariate analysis, Kudo Vi was the only independent predictor of SMIC.

Conclusion

Our data confirm that in LST-NGs size >20 mm, Rectal location, PD morphology, Kudo Vi and JNET2B are strongly associated with increased risk of SMIC, comparable to what shown in Eastern series. Furthermore, these data underline how an accurate optical diagnosis is crucial for establishing the best therapeutic approach.

References

• Bogie RMM, Veldman MHJ, Snijders LARS, et al. Endoscopic subtypes of colorectal laterally spreading tumors (LSTs) and the risk of submucosal invasion: a metanalysis [published correction appears in Endoscopy. 2018 Mar;50(3):C4]. Endoscopy. 2018;50(3):263-282
• Hao XW, Li P, Wang YJ, Ji M, Zhang ST, Shi HY. Predictors for malignant potential and deep submucosal invasion in colorectal laterally spreading tumors. World JGastrointest Oncol. 2022;14(7):1337-1347.
• Ishigaki T, Kudo SE, Miyachi H, et al. Treatment policy for colonic laterally spreading tumors based on each clinicopathologic feature of 4 subtypes: actual status of pseudo-depressed type. Gastrointest Endosc. 2020;92(5):1083-1094.e6
• Pimentel-Nunes P, Libânio D, Bastiaansen BAJ, et al. Endoscopic submucosal dissection for superficial gastrointestinal lesions: European Society of Gastrointestinal Endoscopy (ESGE) Guideline - Update 2022. Endoscopy. 2022;54(6):591-622.
• D’amico F, Amato A, Iannone A, et al. Risk of Covert Submucosal Cancer in Patients With Granular Mixed Laterally Spreading Tumors. Clin. Gastroenterol. Hepatol. 2021.(19):1395–1401.

Introduction

Deep submucosal invasion is not considered an independent risk factor for lymph node metastasis in T1 colorectal cancer (CRC). This study aimed to evaluate the feasibility and effectiveness of diagnostic endoscopic resection for T1 CRCs with deep invasion.

Aims & Methods

This retrospective study included consecutive patients with T1 CRC who underwent either endoscopic submucosal dissection (ESD) or endoscopic mucosal resection (EMR). Pedunculated lesions (Paris classification Ip) were excluded. Low-risk T1 CRCs were defined as lesions with submucosal invasion ≥1000 µm that were resected en bloc with R0 margins and lacked lymphovascular invasion (LVI), high-grade budding (>BD1), or poor differentiation. These lesions were considered eligible for expanded curative resection.

Results

A total of 123 T1 CRC lesions in 121 patients were resected endoscopically (26 by EMR, 97 by ESD). The overall en bloc and R0 resection rates were 89.4% (100/123) and 65.9% (81/123), respectively. For T1b CRCs, these rates were 86.7% (52/60) and 56.7% (34/60). No perforations occurred. Expanded curative resection was achieved in 26.7% (16/60) of T1b cases. Among non-curatively resected T1b lesions, 50.0% (30/60) had LVI, 41.7% (25/60) had positive or indeterminate vertical margins (VM1/VMX), and 13.3% (8/60) showed significant tumor budding.

Conclusion

Diagnostic endoscopic resection for T1 CRCs with deep submucosal invasion is feasible and safe, with a notable rate of expanded curative resection. This strategy may support accurate pathological evaluation and informed treatment planning in selected patients.

Introduction

The ability to achieve endoscopic R0 resection in colorectal T1 cancer depends on the submucosal (SM) invasion distance of the malignancy. In this study, we looked for correlations between the SM invasive distance and achievement of R0 resection.

Aims & Methods

We classified fibrosis of the SM layer as noncancerous (Type B) and cancerous (Type C) and further categorized each into three phases from mild (1) to severe (3). Measurements of SM invasion distances for each tumor were based on the criteria specified by the Japanese Society for Cancer of the Colon and Rectum (JSCCR). For 142 patients (70 male and 72 female, average age of 68.1 years), 143 lesions were diagnosed as cancerous fibrosis in subjects who underwent ESD and 1,813 lesions were scored as colorectal epithelial neoplasms, with T1 cancer being diagnosed by postoperative pathological diagnosis. We evaluated the diagnostic ability of cancerous fibrosis in 308 patients including 165 Type B cases. We also compared the degree of SM invasion in Type C-1, C-2, and C-3 malignancies in which we observed macroscopic typing of the 143 Type C lesions. We then scored the degree of SM invasion in R0 resected Type C lesions. Using an ROC curve and a 95% cutoff index, we calculated the maximal SM invasion distance for which R0 resection could be achieved.

Results

The macroscopic subtypes of Type C lesions were as follows: 0-Is+IIa (LST-G (nodular mixed type)): 55, 0-IIa (LST-NG (flat elevated typ)): 23, 0-IIc+IIa (LST-NG(pseudodepressed typ)): 19, 0-Is: 23, 0-IIa+IIc: 15, 0-IIc: 8. Perioperative endoscopy was able to accurately diagnose 83.9% Type C cases and 93.9% of Type B cases. With regard to diagnostic potential, perioperative endoscopy had 83.9% sensitivity, 93.9%, and specificity. Diagnostic precision was 92.3%, PPV was 92.3%, and NPV was 87.0%. Pathology was used to sub-classify the 143 Type C cases based on severity. Seventy-one patients were C-1, 34 were C-2, and 38 were C-3. The mean SM invasion distances in C-1, C-2 and C-3 cases were 801.2 ± 956.1 mm, 1,745 ± 891.6 mm, and 3063.5 ± 2008.4 mm, respectively; differences between each group were significant (p<0.01). We classified macroscopic types of Type C into Flat and Depressed (FD:0-IIa, 0-IIc+IIa, 0-IIa+IIc, 0-IIc) and Protruded (P: 0-Is+IIa, 0-Is ).Although the corresponding values in the P group were larger (C-1:970.6 mm, C-2:2292.3 mm, and C-3:3483.3 mm, respectively), this difference was not statistically significant. The R0 rate according to the invasive distance was 94.7% when SM was <1,500 mm, and 92.9% when SM was <1,000. For SM between 1,000 mm and 1,500 mm the R0 rate was 19/19 (100%).The percentage of cancer-positive cases in the vertical margin (VM (+)) increased proportionally with the degree of invasion. For SM values between 1,500 and 2,000, VM (+) was 79.2%, whereas for SM values of 2,000 or more, the R0 rate decreased to 45.5%. We identified a statistically significant difference (p=0.037) between less than 1,500 mm and 1,500-2,000 mm. The maximum Youden Index was 0.636 and the R0 rate was 95.4%, when the upper limit was less than 1,625 mm.

Conclusion

An SM of less than 1,625 mm (regardless of the macroscopic type) is predictive of an R0 resection for colorectal T1 cancer, and provided the possibility of curative treatment. Also, we infer that the quantitative and qualitative advantages of ESD can help endoscopists avoid the pitfalls associated with preoperative endoscopic diagnosis, which may be useful in clinical practice.