Introduction

In early-stage colorectal cancer (CRC), distinguishing CRC with deep invasion is crucial in determining subsequent treatments. However, diagnosis remains difficult. Recently, we have developed and reported a computer-aided diagnostic (CAD) system to diagnose CRC with deep invasion, using only non-magnified white light imaging.1) This study aimed to compare the diagnostic accuracy of CAD for early-stage CRC with that obtained in a prospective study using magnified narrow-band imaging endoscopy (M-NBI) and dye-based magnified chromoendoscopy (MCE).2)

Aims & Methods

Among 1173 lesions registered in a multicenter prospective study, 1428 images of 162 early-stage CRC cases (125 Tis CRCs, 16 T1a CRCs and 21 T1b CRCs) registered at our hospital were included. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy rate of the CAD system for diagnosing T1b (depth of invasion ≥1000 μm) CRC were all calculated, and compared with those of M-NBI and MCE diagnoses. Optical diagnoses by M-NBI and MCE were performed by experts in real time.

Results

The sensitivity, specificity, PPV, NPV, and accuracy rate of CAD were 57.1%, 85.8%, 37.5%, 93.1%, and 82.1%, respectively. Whereas those of M-NBI were 71.4%, 93.6%, 62.5%, 95.7%, and 90.2%, respectively, and those of MCE were 85.7%, 91.5%, 60.0%, 97.7%, and 90.7%, respectively. The overall accuracy rate of CAD was significantly lower than those of M-NBI and MCE diagnoses. However, the accuracy rates for depressed lesions (IIa, IIa+IIc) were 87.5% for M-NBI, 81.3% for MCE, and 87.5% for CAD, and for polypoid lesions (Ip, Is) were 83.1% for M-NBI, 84.5% for MCE, and 76.1% for CAD, indicating that the accuracy rates of CAD were similar to those of M-NBI and MCE diagnoses in these cases.

Conclusion

CAD using non-magnified white light imaging is useful for the diagnosis of deep invasive cancer in depressed or polypoidal early-stage CRCs.

References

1) Tokunaga M, Matsumura T, et al. Gastrointest Endosc. 2021;93:647-653.
2) Matsumura T et al. Clin Gastroenterol Hepatol. 2023

Disclosure

This work was supported by JSPS KAKENHI Grant Number 21K07885 and JFE (The Japanese Foundation for Research and Promotion of Endoscopy) Grant.

Introduction

The optical diagnosis of T1 colorectal cancer (CRC) with deep invasion (≥T1b CRC) is crucial in determining subsequent treatment. Recently, computer-aided diagnosis (CADx) has become available for the diagnosis of deep invasive cancer, but until now, it must be combined with image enhanced endoscopy (IEE) or endocytoscopy. We have developed a CADx system to diagnose deep invasive cancer using non-magnified white light imaging (WLI).

Aims & Methods

This study aimed to compare the diagnostic accuracy of the CADx in T1 CRC diagnosis with that of non-expert endoscopists and expert endoscopists. A total of 365 images of 37 T1 CRCs (16 T1a CRCs and 21 T1b CRCs) from prospectively enrolled consecutive patients were included in the study. Images were independently diagnosed by two non-expert endoscopists and two expert endoscopists; sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy of T1b CRC diagnosis by the CAD system were calculated and compared with the endoscopists diagnostic accuracies.

Results

The sensitivity, specificity, PPV, NPV, and accuracy of CAD were 70.2%, 60.4%, 84.2%, 49.3%, and 70.7%, respectively, while those of non-experts were 39.9%, 80.6%, 82.7%, 36.6%, and 51.9%, respectively. The accuracy rate was significantly higher in the CAD group (p < 0.01). On the other hand, those of experts were 47.9%, 87.7%, 79.2%, 63.2%, and 67.7%, respectively, which were comparable to the diagnostic accuracy of CAD. The diagnostic time per image was significantly shorter for CAD than for endoscopists (0.49 sec. for CAD, 7.72 sec. for non-expert, and 5.77 sec. for expert, p < 0.01, p < 0.01, comparison with CAD).

Conclusion

Non-magnified WLI-based CADx is useful for non-expert endoscopists in diagnosing T1 CRC with deep invasion.

Disclosure

This work was supported by JSPS KAKENHI Grant Number 21K07885 and JFE (The Japanese Foundation for Research and Promotion of Endoscopy) Grant.

Introduction

Improving the adenoma detection rate (ADR) can contribute to reducing the incidence and mortality of post-colonoscopy colorectal cancer (PCCRC). Texture and color enhancement imaging (TXI) enhances subtle tissue textures, selectively brightens dark areas, and emphasizes the differences between red and white colors^1,2. Several studies have investigated the visibility and color differences of TXI in vitro and reported its superiority over WLI^3-7. However, A few studies have evaluated the ADR of colonoscopy with TXI, which is a novel image-enhancing technology. This study aims to compare the detection of colorectal polyps using TXI to that using white light imaging (WLI).

Aims & Methods

This study was conducted retrospectively in a single center using propensity-matched scoring based on the patients’ baseline characteristics, such as age, sex, indication, bowel preparation, endoscopist, colonoscope type, and withdrawal time. This study compared the effectiveness of WLI and TXI in patients who underwent chromocolonoscopy with indigo carmine spraying. The study determined the differences in the adenoma, including high-risk adenoma, and sessile serrated lesion (SSL) detection rates and the mean number of detected adenomas and SSLs per colonoscopy between the TXI and WLI groups. High-risk adenomas were defined as three or more adenomas, an adenoma ≥10 mm, an adenoma with a villous component, and an adenoma with high-grade dysplasia. The Wald test with logistic regression was used to analyze the P values.

Results

After propensity score matching, 1970 patients were enrolled into each imaging modality group. The mean patient age was 57.2 ± 12.5 years, and 44.5% of the cohort were men. The ADR was higher in the TXI group than in the WLI group (55.0% vs. 49.4%, odds ratio: 1.25). High-risk ADR were more common in the TXI group than in the WLI group (17.6% vs. 12.8%; OR: 1.45). The mean number of adenomas per colonoscopy (APC) was higher in the TXI group than in the WLI group (1.187 vs. 0.943, OR: 1.12). APC with a 0-II morphology according to the Paris classification (1.093 vs. 0.848, OR: 1.14) and APC of <6 mm (0.992 vs. 0.757, OR: 1.16) were higher in the TXI group than in the WLI group. The adenoma plus SSL detection rate (ASDR) was higher in the TXI group than in the WLI group (58.8% vs. 53.2%, OR: 1.25). The mean number of adenomas plus SSLs per colonoscopy (ASPC) was greater in the TXI group than in the WLI group (1.287 vs. 1.025, OR: 1.13, Table).

Conclusion

A randomized controlled trial⁸ and a cross-over study⁹ previously showed that the ADR of TXI was higher than that of WLI. In this study, we found that the ADR, high-risk ADR, APC, ASDR, and ASPC of TXI were higher than those of WLI after propensity-score matching of patients who underwent chromoendoscopy. TXI may help prevent PCCRC.

References

1 Sato T. TXI: Texture and Color Enhancement Imaging for Endoscopic Image Enhancement. J Healthc Eng 2021; 2021.
2 Tani Y, et al. Gastrointestinal: Texture and color enhancement imaging is useful for detection of small gastric adenocarcinoma of fundic-gland type. J Gastroenterol Hepatol 2024.
3 Nishizawa T, et al. TXI (Texture and Color Enhancement Imaging) for Serrated Colorectal Lesions. J Clin Med 2021.
4 Toyoshima O, et al. Texture and color enhancement imaging in magnifying endoscopic evaluation of colorectal adenomas. World J Gastrointest Endosc 2022.
5 Tamai N, et al. Visibility evaluation of colorectal lesion using texture and color enhancement imaging with video. DEN Open 2022.
6 Yoshida N, et al. Analysis of Texture and Color Enhancement Imaging for Improving the Visibility of Non-polypoid Colorectal Lesions. Dig Dis Sci 2022.
7 Hiramatsu T, et al. Improved visibility of colorectal tumor by texture and color enhancement imaging with indigo carmine. World J Gastrointest Endosc 2023.
8. Antonelli G, et al. Texture and color enhancement imaging versus high definition white-light endoscopy for detection of colorectal neoplasia: a randomized trial. Endoscopy 2023.
9. Sakamoto T, et al. Detection of colorectal adenomas with texture and color enhancement imaging: Multicenter observational study. Dig Endosc 2023.

Disclosure

​Nothing

Introduction

Colorectal cancer’s (CRC) incidence above 50 years old has been decreasing globally in the last decades, but its incidence in patients below 50 years old (early-onset colorectal cancer, EO-CRC) has been increasing, for reasons not yet fully understood.

Aims & Methods

A unicentric cohort study was conducted in a tertiary centre, including all patients admitted for a first diagnosis of CRC and evaluated by the Multidisciplinary Colorectal Cancer Group from 01.01.2017 until 31.12.2018. Patients with a previous diagnosis of a Hereditary Colorectal Cancer Syndrome were excluded.

Results

A total of 438 patients were included, 58.2% males, with a mean age at diagnosis of 67.7±11.1 years old. Mean follow-up time was 41.49 months. There were 25 EO-CRC patients (5.7%), 17 males (68%), mean age 43.1±6.0 years old.
Globally, 32.4% of the patients were current or past smokers, 18.5% had previous non-colorectal cancer, 7.5% and 3.4% were previously exposed to immunosuppressive drugs or abdominal/pelvic radiotherapy, respectively. The majority presented with normal(29.7%) to high Body Max Index (39.7%), median 25.6 (IQR:22.6-28.4) Kg/m². The most common CRC location was the rectum (42.9%) and 56.1% were stage I or II (AJCC 8^th edition).
In the univariate analysis, a significant association was found between EO-CRC and: smoking status (past or current smokers 52% in EO-CRC vs. 31.2% in older cases p=0.009); lymphovascular invasion (40.0% in EO-CRC vs. 17.4% in over 50, p=0.018) No significant differences were found for histological subtype (p=0.447), perineural invasion (p=0.474), or tumor stage at diagnosis, although a relevant proportion of the younger patients had metastatic disease at diagnosis (28.0% vs. 12.8%, p=0.064).
Immunohistochemistry for mismatch-repair proteins showed loss of expression of at least one protein in 1/18 EO-CRC patients and 22/179 of older patients (p=0.728).
From the EO-CRC patients, 16 were evaluated in the Familial Cancer Clinic and 14 underwent germline mutation analysis: 13 patients had inconclusive results, one of them presented a MUTYH heterozygote mutation and another was diagnosed with MUTYH-associated Polyposis (composed heterozygote mutation).

Conclusion

Colorectal cancer showed distinctive features in the younger population, with a higher prevalence of lymphovascular invasion and, possibly, a higher incidence of metastatic disease at diagnosis. Smoking had a significant association with CRC, especially in this younger population. Whether this means there is a biological difference is not yet clear. More evidence is needed in order to clarify EO-CRC aetiology and to develop screening and improve management strategies.

References

Siegel RL, Jakubowski CD, Fedewa SA, Davis A, Azad NS. Colorectal Cancer in the Young: Epidemiology, Prevention, Management. Am Soc Clin Oncol Educ Book. 2020 Mar;40:1-14. doi: 10.1200/EDBK_279901. PMID: 32315236

Introduction

Screening colonoscopy reduces colorectal cancer (CRC) mortality. However, several studies have reported a lower participation rate of colonoscopy. Now it is important to provide less invasive test for CRC screening.
AminoIndex® Cancer Risk Screening (AICS®) is an examination that measures plasma amino acid concentrations and estimates the risk of existing CRC based on the difference in amino acid balance in patients with CRC and healthy individuals. AICS is calculated from 0.0 to 10.0 with the higher value indicating a higher the risk of existing CRC.
We aimed to conduct a prospective cohort study to evaluate the accuracy of AICS® in detecting the risk probability for early colorectal lesions, such as advanced adenoma (AA), intramucosal neoplasia (Tis), or T1 CRC.

Aims & Methods

Consecutive patients who underwent colonoscopy between 06/02/2017 and 31/03/2021at the National Cancer Center Central Hospital and endoscopically diagnosed adenoma larger than 20 mm, intramucosal neoplasia (Tis), or submucosal invasive carcinoma (T1) were included as a selection criterion. Patients with endoscopically suspected intramucosal neoplasia or high-grade dysplasia by preoperative colonoscopy, but finally diagnosed with adenoma were also included in the study. We excluded the following patients; 1) patients with polyposis such as familial colorectal adenomatosis or inflammatory bowel disease, 2) patients with concurrent cancer of other organs, 3) patients with obvious bleeding, 4) patients with severe defecation disorder, and 5) patients with stenosis of colon or intestine.
We measured plasma amino acid concentrations calculated the AICS score. FIT was also measured at the same time. The lesions were endoscopically resected using EMR or ESD technique. The sensitivity of AICS, FIT, and the combination of FIT and AICS were examined according to the pathological diagnosis.

Results

Two hundred and seventeen patients were included in the primary analysis, and 208 patients excluding 9 patients who did not perform FIT were included in the secondary analysis.
The median age of the 217 patients was 71 years old (range: 32- 91). The mean lesion size was 28.9 mm±12.9. Prevalence of AA, Tis, T1, and advanced lesion was, 63, 118, 30, and 6, respectively. Six lesions were suspected to be T1 carcinoma on preoperative endoscopy, following pathological examination revealed advanced cancer after endoscopic resection. The sensitivity of AICS for the advanced neoplasia (AN), AA, intramucosal neoplasia (Tis), submucosal invasive carcinoma, and advanced CRC was 28.1％, 30.9%, 25.4%, 23.3%, and 33.3%, respectively.
In the secondary endpoint, the sensitivity of FIT for AN, AA, intramucosal neoplasia (Tis), submucosal invasive carcinoma, and advanced CRC was 47.0%, 35.3%, 49.1%, 46.7%, and 100%, respectively. The sensitivity of the combination of FIT and AICS for AN, AA, intramucosal neoplasia (Tis), submucosal invasive carcinoma, and advanced CRC was 61.1％, 52.9%, 64.0%, 60.0%, 100%, respectively.

Conclusion

Although it was a reasonable value compared to the development data, AICS® has insufficient sensitivity for lesions requiring endoscopic intervention. It could be clinically applicable as a minimally invasive examination to stratify the risk of existing CRC in combination with FIT for colorectal screening.

Disclosure

The primary investigator (Hiroyuki Takamaru) had received research funding from Ajinomoto Co. Ltd.

Introduction

Colorectal cancer (CRC) is one of the most common malignancies worldwide, and early detection significantly improves patient outcomes. Long non-coding RNAs (lncRNAs) are >200 nucleotide transcripts that regulate gene expression and are frequently dysregulated in cancer. Notably, certain lncRNAs are overexpressed during colorectal tumorigenesis and detectable in circulation, making them promising non-invasive biomarkers. This study aimed to identify circulating lncRNAs with progressive expression changes along the adenoma-carcinoma sequence and evaluate their potential as early diagnostic markers for CRC.

Aims & Methods

We performed bioinformatic screening of three public gene expression datasets (GSE117606, GSE289499, GSE154548) containing colorectal normal, adenoma, and carcinoma tissues. Twelve lncRNA candidates showing linear differential expression across the adenoma-to-carcinoma sequence were identified. The five most significantly dysregulated lncRNAs (ZFAS1, FOXP4-AS1, CRNDE, UCA1, SNHG17) were selected for further validation. Plasma samples were collected from healthy controls (n=21), patients with advanced adenomas (precancerous lesions, n=51), early-stage CRC (Tis-T1, n=24), and advanced CRC (T2-T4, n=53). Levels of the five lncRNAs in plasma were measured by quantitative PCR and normalized to 5S rRNA using the 2^-ΔCt method. Expression trends across the four groups were analyzed. Receiver operating characteristic (ROC) curves (area under the curve, AUC) were generated to assess the ability of individual lncRNAs to distinguish early CRC from controls. A logistic regression model was used to combine multiple lncRNAs into a panel and evaluate its diagnostic performance (sensitivity and specificity).

Results

Bioinformatic analysis identified 12 lncRNAs with stepwise expression changes from adenoma to carcinoma, and the top five candidates were successfully measured in plasma. Among these, UCA1 and SNHG17 showed progressively increasing plasma levels from healthy controls to adenoma to early CRC, with the highest levels in advanced CRC (trend P<0.05). In contrast, CRNDE levels remained unchanged between healthy and early CRC groups but rose significantly in advanced CRC, suggesting its upregulation is associated with tumor progression. The other two lncRNAs (ZFAS1, FOXP4-AS1) exhibited less pronounced changes. In diagnostic tests, UCA1 alone distinguished early-stage CRC from controls with an AUC of 0.82, whereas SNHG17 achieved an AUC of 0.73. Notably, a combined three-lncRNA panel (UCA1 + SNHG17 + CRNDE) improved early CRC detection, achieving an AUC of 0.85 with 87.5% sensitivity and 61.9% specificity for differentiating early CRC from healthy individuals. This multi-marker panel outperformed any single lncRNA biomarker in identifying early CRC.

Conclusion

A GEO dataset-guided approach coupled with plasma validation provided robust evidence that circulating lncRNAs have significant diagnostic potential for CRC. UCA1 and SNHG17 emerged as promising blood-based markers for early detection of colorectal neoplasia, while CRNDE may serve as a complementary marker indicative of advanced disease progression. Moreover, a panel combining these lncRNAs demonstrated superior accuracy over individual markers, underscoring the value of a multi-lncRNA approach. These findings support further development of non-invasive, lncRNA-based blood tests for early colorectal cancer screening.

Introduction

Surgery is the standard treatment for colorectal cancer (CRC). Following the introduction of screening programs for CRC, a substantial shift toward the diagnosis of CRC at an earlier stage is observed (1). In T1 CRC merely 10% of carcinomas have spread to lymph nodes or distant organs (2), suggesting that a vast majority of T1 CRC can be successfully treated with a minimal invasive approach. Endoscopic treatment for early CRC (pT1), rather than surgical resection, is expected to reduce mortality, morbidity and costs (3, 4). We evaluated oncological outcomes and patient safety of endoscopic resection of suspected pT1 CRC in a Norwegian CRC screening centre.

Aims & Methods

From January 2020 until November 2022, we prospectively registered all endoscopic procedures performed for suspected pT1 CRC. We recorded endoscopic technique, optical evaluation, pathology results, staging using CT and MRI, additional surgery as well as complications and final outcome. All patients were informed about the advantages and potential risks of endoscopic treatment vs. surgical resection, and all gave informed consent before treatment after shared decision-making. All patients were discussed at our multidisplinary team (MDT) meeting.

Results

A total of 42 suspected T1 CRC cases treated endoscopically were included. 95% (38/40) of the lesions were identified as possibly malignant with optical evaluation (JNET 2B/NICE III/SANO IIIa) before treatment. 62% (26/42) of patients were deemed to have completed treatment with endoscopic resection. Sixteen patients underwent surgery following endoscopic treatment after discussions in the MDT meeting. Of these, three had lymph node metastasis, one of these had both lymph node metastasis and residual disease; at the site of the primary tumor. All three patients had one or more histopathological risk factors (one T2 stage + lymphovascular invasion (LVI) + poor differentiation, one T1 with LVI, one T1 with Rx and LVI). The remaining 13 patients (81% of those operated) had no residual disease and were thus overtreated. No severe adverse events were recorded, and no patients needed hospitalization with intensive care treatment.

Conclusion

Our study suggests that endoscopic treatment of suspected early-stage CRC is efficient and safe.

References

1. Cardoso R, Guo F, Heisser T, Hackl M, Ihle P, De Schutter H, et al. Colorectal cancer incidence, mortality, and stage distribution in European countries in the colorectal cancer screening era: an international population-based study. Lancet Oncol. 2021;22(7):1002-13.
2. Ichimasa K, Kudo S-E, Miyachi H, Kouyama Y, Misawa M, Mori Y. Risk Stratification of T1 Colorectal Cancer Metastasis to Lymph Nodes: Current Status and Perspective. Gut and Liver. 2021;15(6):818-26.
3. Vermeer NCA, Backes Y, Snijders HS, Bastiaannet E, Liefers GJ, Moons LMG, et al. National cohort study on postoperative risks after surgery for submucosal invasive colorectal cancer. BJS open. 2018;3(2):210-7.
4. Ma C, Teriaky A, Sheh S, Forbes N, Heitman SJ, Jue TL, et al. Morbidity and Mortality After Surgery for Nonmalignant Colorectal Polyps: A 10-Year Nationwide Analysis. Am J Gastroenterol. 2019;114(11):1802-10.

Disclosure

Michael Bretthauer Olympus, Cybernet, Paion
Svein Oskar Frigstad Takeda, Galapagos, Jansen-Cilag, Abbvie, Pharmacosmos, Norgine and Bristol-Myers-Squibb