Introduction

In the carcinogenic pathway of colorectal cancer, the first concept is the "adenoma-carcinoma sequence" and the second concept is the " serrated pathway ". In these concepts, adenomas and serrated lesions gradually progress to cancer. The third concept is the "de novo pathway," in which cancer develops without adenomas or serrated lesions and is also characterized by high malignancy and rapid progression. We have endoscopically characterized depressed colorectal cancers considered to be of the "de novo pathway" and validated the usefulness of pit pattern and EC classification.

Aims & Methods

A total of 50119 colorectal neoplasms were resected endoscopically or surgically in our institution from April 2001 to December 2023. They were subjects of this study. Advanced cancers were excluded. Of these, 1633 lesions were submucosally invasive (T1) carcinomas, 6802 lesions were classified as high-grade dysplasia and 38952 lesions as low-grade dysplasia. Morphologically, they were divided into 3 types: depressed, flat, and protruded type comprising 1.1 (%), 45.0 (%),and 54.0（%), respectively. Specifically, the distinctive features of depressed type neoplasms concerning their pit pattern and EC classification were examined.

Results

Most of the flat (91.5%) and protruded type (94.9%) lesions showed type IIIL or IV pit pattern, which are common findings in adenomas. On the other hand, most of the depressed type lesions (92.3%) classified as type IIIs, VI or VN pit patterns, are typically seen in carcinomas. As for endocytoscopy, most of flat and protruded type lesions were identified as EC2 corresponding to adenomas. In contrast, relatively high rates of depressed type lesions were categorized as EC3a (40.3%) and EC3b (52.3%), consistent with invasive carcinomas.
The proportion of T1 carcinomas in depressed type lesions was 60.0%, whereas in flat and protruded type lesions it was 2.7% and 2.6%, respectively. Additionally, 11.6% of depressed type lesions less than 5mm in diameter were T1 carcinomas, whereas flat and protruded type lesions were 0.01% and 0%, respectively.

Conclusion

This study revealed that depressed lesions were classified as type IIIs, VI or VN pit patterns on magnifying endoscopy and as type EC3a or EC3b on endocytoscopy. Lesions with these features or pit patterns tend to invade the submucosal layer even if they are small size. Despite their high potential for malignancy, depressed lesions are often ignored. However, it is critical to recognize their features and accurately diagnose lesions based on morphology, pit pattern, and EC classification.

Introduction

In the carcinogenic pathway of colorectal cancer, the first concept is the "adenoma-carcinoma sequence" and the second concept is the " serrated pathway ". In these concepts, adenomas and serrated lesions gradually progress to cancer. The third concept is the "de novo pathway," in which cancer develops without adenomas or serrated lesions and is also characterized by high malignancy and rapid progression. We have endoscopically characterized depressed colorectal cancers considered to be of the "de novo pathway" and validated the usefulness of pit pattern and EC classification.

Aims & Methods

A total of 54819 colorectal neoplasms were resected endoscopically or surgically in our institution from April 2001 to December 2024. They were subjects of this study. Advanced cancers were excluded. Of these, 1694 lesions were submucosally invasive (T1) carcinomas, 7330 lesions were classified as high-grade dysplasia and 39977 lesions as low-grade dysplasia. Morphologically, they were divided into 3 types: depressed, flat, and protruded type comprising 1.0 (%), 46.4 (%),and 52.6（%), respectively. Specifically, the distinctive features of depressed type neoplasms concerning their pit pattern and EC classification were examined. EC classification is a classification for an endocytoscopy that can evaluate pathology, such as nuclear atypia and glandular structure, by magnifying stained cells. EC1a is diagnosed as normal mucosa, EC1b is diagnosed as hyperplastic polyps, and if slit-like glandular ducts or spindle-shaped nuclei are present, it is classified as EC2 and diagnosed as an adenoma or intramucosal carcinoma. If irregularly shaped glandular ducts or nuclei with a high N/C ratio are found, it is classified as EC3a, and diagnosed as intramucosal carcinoma or SM lightly invasive carcinoma. If the glandular ducts are indistinct and the nucleus is irregularly shaped and darkly stained, it is classified as EC3b and diagnosed as SM highly invasive carcinoma.

Results

Most of the flat (91.5%) and protruded type (94.9%) lesions showed type IIIL or IV pit pattern, which are common findings in adenomas. On the other hand, most of the depressed type lesions (92.6%) classified as type IIIs, VI or VN pit patterns, are typically seen in carcinomas. As for endocytoscopy, most of flat and protruded type lesions were identified as EC2 corresponding to adenomas. In contrast, relatively high rates of depressed type lesions were categorized as EC3a (40.3%) and EC3b (52.4%), consistent with invasive carcinomas.
The proportion of T1 carcinomas in depressed type lesions was 58.7%, whereas in flat and protruded type lesions it was 2.5% and 2.5%, respectively. Additionally, 12.0% of depressed type lesions less than 5mm in diameter were T1 carcinomas, whereas flat and protruded type lesions were 0.01% and 0%, respectively.

Conclusion

This study revealed that depressed lesions were classified as type IIIs, VI or VN pit patterns on magnifying endoscopy and as type EC3a or EC3b on endocytoscopy. Lesions with these features or pit patterns tend to invade the submucosal layer even if they are small size. Despite their high potential for malignancy, depressed lesions are often ignored. However, it is critical to recognize their features and accurately diagnose lesions based on morphology, pit pattern, and EC classification.

Disclosure

Shin-ei Kudo and Masashi Misawa received speaking honoraria from Olympus Corporation and have an ownership interest of the products of Cybernet Systems. Tetsuo Nemoto received a research grant from Olympus Corporation for other studies. Other authors have nothing to declare.

Introduction

Multiple pathways have been proposed to explain the development of colorectal cancer. The first is the well-established adenoma–carcinoma sequence, in which polypoid adenomas gradually progress to early polypoid cancers and eventually to advanced carcinomas. The second is the serrated pathway, where serrated lesions evolve into early cancers. The third is the de novo pathway, which hypothesizes that carcinomas arise directly from normal epithelium without a pre-existing adenomatous stage. This study focuses on the depressed-type colorectal cancers, which are thought to develop through the de novo pathway, and aims to elucidate their distinct clinicopathological features.

Aims & Methods

From April 2001 to December 2023, a total of 50,119 colorectal neoplasms (excluding advanced cancers) were resected either endoscopically or surgically at Showa University Northern Yokohama Hospital. Among them, 1,633 lesions were identified as T1 carcinomas. Based on macroscopic growth patterns, these T1 cancers were classified into three categories: depressed-type (n = 323; 20.1%), flat-type (n = 602; 36.9%), and protruded-type (n = 703; 43.0%). We compared the pathological characteristics and recurrence rates among the three groups.

Results

The mean tumor size was 15 mm in depressed-type lesions, 32 mm in flat-type, and 18 mm in protruded-type. Vascular invasion was significantly more frequent in the depressed-type group (42%) compared to both flat- and protruded-type lesions (21% each). The proportion of poorly differentiated or mucinous adenocarcinoma was also higher in the depressed type (14%) compared to flat (10%) and protruded types (15%). In contrast, the prevalence of adenomatous components was markedly lower in the depressed type (4%) than in the flat (54%) and protruded types (52%). Similarly, the frequency of polypoid morphology was only 13% in depressed lesions, compared to 56% and 88% in flat and protruded types, respectively. These findings suggest that depressed-type lesions may arise directly from normal epithelium, bypassing the adenomatous phase. The overall rate of distant metastasis or recurrence among all T1 cancers was low, at 0.8% (13 out of 1,633 cases).

Conclusion

Depressed-type colorectal carcinomas are characterized by significantly smaller tumor size and a lower prevalence of adenomatous components, yet exhibit a higher rate of vascular invasion and unfavorable histological features compared to flat and protruded types. These clinicopathological features support the hypothesis that depressed-type carcinomas follow a de novo pathway of tumorigenesis. Given their subtle appearance and high malignant potential, these lesions may be overlooked during routine colonoscopy. Therefore, careful attention should be paid to their morphological features during endoscopic examination to ensure early detection and appropriate management.

Introduction

Several development concepts have been proposed for colorectal neoplasms in the carcinogenesis of colorectal cancer. One is “adenoma-carcinoma sequence”. In this concept, polypoid adenoma develops into early polypoid cancer and finally develops to advanced cancer. One is “serrated-pathway”. In this concept, serrated lesion develops into early cancer. The other is “de novo” pathway. In this concept, early cancers develop without preexisting adenoma. We investigated clinicopathological characteristics of depressed-type colorectal carcinomas considered as “de novo” pathway.

Aims & Methods

A total of 50119 colorectal neoplasms excluding advanced cancers were resected endoscopically or surgically in our center from April 2001 to December 2023 at Showa University Northern Yokohama Hospital. Of these, 1633 lesions were T1 cancers. According to the developmental morphology classification, they were divided into 3 types: 323 lesions (20.1%) were depressed-type, 602 lesions (36.9%) were flat-type and 703 lesions (43.0%) were protruded-type. We analyzed the pathological difference and recurrence of these types.

Results

The average tumor size were 15mm, 32mm, and 18mm in depressed-type, flat-type and protruded-type lesions, respectively. The rates of vessel invasion were 42%, 21% and 21%, that of poorly differentiated or mucinous adenocarcinoma were 14%, 10% and 15% in depressed-type, flat-type and protruded-type lesions, respectively. The rates of these pathological factors were significantly higher in depressed-type lesions than other types. On the other hand, the rates of adenomatous component were 4%, 54% and 52%, and the rates of polypoid growth were 13%, 56% and 88%, respectively. These rates were significantly lower in depressed-type lesions than other types, suggesting that they emerge directly from normal epithelium without going through the adenomatous stage. The rate of distant metastasis or recurrence was observed in 0.8% (13/1633).

Conclusion

Depressed-type colorectal carcinomas had significantly lower adenomatous components and smaller size than flat-types or protruded-types, and they also contained worth pathological features than other types. So, depressed colorectal carcinoma can be the important lesions for clinical diagnosis. Therefore, during routine colonoscopy, we should give a greater attention to the morphological features of the depressed-type colorectal carcinomas.

Introduction

Computer-aided detection (CADe) systems improve adenoma detection rate (ADR). However, there is some concern that the long-term use of CADe systems might lead to a decline in endoscopists’ independent detection skills, particularly their ability to detect lesions without assistance—a phenomenon referred to as "deskilling".

Aims & Methods

This study aims to evaluate the impact of CADe on the learning curve of endoscopists for ADR. This was a propensity score–matched (PSM), prospective, single-center, observational study conducted at a tertiary care hospital from January 2021 to December 2023. CADe systems were installed in half of the endoscopy units, and patients were equally distributed between the rooms. Patients in CADe-equipped rooms were examined using EndoBRAIN-EYE (Olympus Corp, Tokyo, Japan). Patients aged ≥ 20 years scheduled for colonoscopy were included, excluding those with polyposis, inflammatory bowel disease, known polyps, incomplete colonoscopy, emergency cases, previous colorectal surgery, and examination by novices. Endoscopists were classified as high-detectors (ADR ≥ 25%) or low-detectors (ADR < 25%) based on the ADR recorded before CADe implementation. The primary outcome was to evaluate the learning effect of CADe using cumulative summation (CUSUM) analysis based on ADR during both CADe and non-CADe procedures to assess skill acquisition and transfer. The CUSUM scores were calculated from the acceptable probability of failure and unacceptable probability of failure. Acceptable and unacceptable ADR were defined as 40% and 30% for high detectors, and 35% and 25% for low detectors, respectively. Performance was judged based on the boundary lines (h0 and h1): acceptable if the CUSUM plot fell below h0, unacceptable if it went above h1, and inconclusive requiring further observation if it stayed between these boundaries. The secondary outcomes included ADR, advanced adenoma detection rate (AADR), and sessile serrated lesion detection rate (SSLDR). The study received ethics approval (no.19H072) and complied with the Declaration of Helsinki.

Results

Out of 5,717 patients initially enrolled, 4,712 patients (2,356 in CADe group and 2,356 in non-CADe group) were analyzed after PSM for known factors (age, sex, indication, and bowel preparation). During CADe-assisted procedures, both high-detectors and low-detectors showed patterns below the acceptable performance line (h0), indicating improved adenoma detection performance with AI support. However, during non-CADe procedures, the patterns diverged significantly. For high-detectors, their CUSUM plots consistently fell below the acceptable performance line (h0) over time during non-CADe colonoscopies, indicating that they successfully acquired and maintained improved adenoma detection skills even without AI assistance. In contrast, the CUSUM plots of the low-detectors remained between the acceptable (h0) and unacceptable (h1) limits throughout the study period, showing no significant change in learning trajectory during non-CADe procedures. The CADe group had a significantly higher ADR (40.5% [95% CI: 38.5-42.5%]) compared to non-CADe group (32.4% [95% CI: 30.5-34.4%]; p < 0.001). SSLDR was also significantly higher in the CADe group (6.9% [95% CI: 5.9-8.0%] vs. 4.5% [95% CI: 3.7-5.4%]; p = 0.001), while AADR showed no significant difference (4.1% [95% CI: 3.4-5.0%] vs. 4.7% [95% CI: 3.9-5.6%]; p = 0.39).

Conclusion

The implementation of the CADe system did not result in deskilling regarding adenoma detection.

Disclosure

The conflict of interests were following: Shin-ei Kudo and Masashi Misawa received speaking honoraria from Olympus Corporation and have an ownership interest of the products of Cybernet Systems. Kensaku Mori received research grants from Cybernet Systems, Morita Mfg, Atom Medical Inc, and Asahi Intecc. Additionally, Kensaku Mori serves as a Technical Advisor for Sanyu Industry. Tetsuo Nemoto received a research grant from Olympus Corporation for other studies. Other authors have nothing to declare.