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) screening reduces cancer risk, yet real-world adherence to screening remains variable. We aimed to leverage a large healthcare organization longitudinal cohort to evaluate factors that influence the timeliness of adherence to screening guidelines.

Aims & Methods

We included average-risk Maccabi Healthcare Services members aged 50–75 years who were alive on 1 January 2025. Demographics, comorbidities, hemoglobin values, and dates of fecal immunochemical test(FIT), CT-colonography (CTC) and colonoscopy were extracted.
Adherence was defined as annual FIT, colonoscopy every 10 years, or CTC every 5 years.
Patients covered for >50 % versus ≤50 % of follow-up time by screening guidelines were compared with Wilcoxon rank-sum (continuous) and χ²/Fisher’s exact (categorical) tests.
In order to study factors associated with adherence times, longitudinal adherence was modelled with a gap-time Andersen–Gill Cox regression. The dependent variable was time (in periods) to the recurrent event active adherence. Adjusted hazard ratios (HRs) and 95 % confidence intervals (CI) were estimated with robust variance, clustering on patient ID to account for within-subject correlation.

Results

Our cohort comprised 590,550 adults at screening age, contributing 6,581,044 person-years of follow-up. In a baseline comparison between individuals whose proportion of time covered was less than 50%(n=282,347) vs more than 50%(n=308,203), the latter group was older (60.00 [55.00, 68.00] years vs 62.00 [57.00, 67.00] years, p-value<0.001) with a longer median follow up (9.0 [4.0, 17.0] years vs 11.0 [6.0, 16.0] years, p-value<0.001). Higher prevalence of hypertension (17.5 % vs 12.0 %, p-value<0.001), diabetes mellitus (8.2 % vs 5.8 %, p-value<0.001), pre-diabetes (22.4 % vs 17.5 %, p-value<0.001), and cardiac disease (4.8 % vs 3.4 %, p-value<0.001) were seen among the more compliant group. Consistent with greater adherence, endoscopic referral was more common at baseline in the more compliant group (6.2 % vs 1.0 %, p-value<0.001). Interestingly. Although the differences in distributions of sector, district and socioeconomic rank categories were significant, the absolute percentage differences across strata were small and unremarkable (<3 percentage points for any category).
A gap-time survival model demonstrated that each additional year of age was associated with longer intervals and a lower aHR for active adherence (aHR 0.94, 95 % CI 0.94–0.94). Men undergone screening tests marginally sooner than women (aHR 1.05, 95% CI 1.04–1.05). Adherence was lower in the orthodox sector (aHR 0.84, 95% CI 0.84–0.85). Metabolic or cardiovascular conditions translated into earlier adherence: pre-diabetes (aHR 1.63, 95% CI 1.62-1.63), diabetes (aHR 1.54, 95% CI 1.54-1.55), hypertension (aHR 1.22, 95% CI 1.21-1.23), cardiac disease (aHR 1.14, 95% CI 1.14-1.15), and obesity (aHR 1.10, 95% CI 1.10-1.11). Severe conditions and subjects included in severe disease registry were associated with lower adherence (aHR 0.33, 95% CI 0.30-0.38; and aHR 0.63, 95% CI 0.59-0.67, respectively). Recent higher hemoglobin levels delayed active adherence (aHR 0.97 per each increase of 1 g/dL, 95% CI 0.97-0.98).

Conclusion

Our results suggest that long term compliance for CRC screening is related to age as well as for chronic medical conditions, particularly metabolic and cardiovascular. Screening efforts should therefore be aimed at healthy subjects or those with minor contact with medical providers.

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

Colorectal cancer (CRC) screening is well established worldwide. However, the suboptimal sensitivity of the Fecal Immunochemical Test (FIT) for precancerous lesions justifies the search for new tools, namely microRNAs (miRs). In recent years, the detection of these molecules in liquid biopsies has gained increasing interest, as they reflect CRC progression and enable the early detection of precancerous lesions. Moreover, using miRs as a blood-based screening test could potentially increase patient adherence.

Aims & Methods

In this context, we aimed to identify circulating miR profiles for the early detection of CRC. Based on our previous literature review, we selected four miRs (miR-21-5p, miR-92a-3p, miR-451a and miR-199a-5p) with the best performance for the detection of CRC and high-grade dysplasia lesions (HGD). MiR expression was evaluated using RT-qPCR in plasma samples from 80 individuals who underwent colonoscopy with different clinical outcomes, namely, individuals without lesions found on colonoscopy, low-grade dysplasia lesions, high-grade dysplasia lesions, and patients diagnosed with CRC.

Results

Our findings demonstrate a decreased expression of all miRs in CRC and HGD lesions. Regarding HGD identification, miR-21-5p demonstrate a sensitivity of 68% (95% CI: 46 – 85%) and a specificity of 100% (95% CI: 84 – 100). Moreover, miR-92a-3p, miR-451a and miR-199a-5p demonstrated a sensitivity higher than 85% for HGD lesions detection, despite low sensitivity (around 70%). Concerning CRC detection, miR-92a-3p and miR-199a-5p demonstrated sensitivity of approximately 65%, with specificities of 70%, for miR-92a-3p (95% CI: 48 – 85%), and 80% for miR-199a-5p (95% CI: 58 – 92%). Furthermore, miR-21-5p showed outstanding performance in CRC identification with a sensitivity of 95% (95% CI: 75 – 100%), for an AUC of 0.900 (95% CI: 0.807 – 0.993). Moreover, when a negative result was obtained for one of these miRs, the presence of colorectal cancer lesions could be accurately excluded (negative predictive value: 98%).

Conclusion

These findings suggest that circulating miRs have the potential to improve the detection of precancerous lesions, surpassing the performance of FIT. Moreover, given their accuracy in identifying individuals without lesions, they could serve as effective confirmatory screening tools, reducing the number of unnecessary colonoscopies.
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Introduction

Colorectal cancer (CRC) can be divided into screen-detected and non-screen-detected CRC. Furthermore, based on the interval between CRC detection and a previous screening or examination, CRC can be classified into several groups, including interval cancer and post-colonoscopy CRC. The proportion and characteristics of each CRC need to be clarified to understand the usefulness and limitations of CRC screening; however, they have not been fully elucidated. Particularly, little data is available on interval cancer under the annual fecal immunochemical test (FIT) screening.

Aims & Methods

We aimed to examine the proportions and characteristics of CRC with different detection histories by conducting a multicenter prospective study in Japan (“C-DETECT study”). Consecutive adult patients with CRC were prospectively enrolled in four hub hospitals of cancer treatment. CRC detection methods and intervals from previous examinations were assessed using a questionnaire. Since the population-based CRC screening using an annual FIT is performed in Japan, FIT-interval cancer was defined as CRC detected within 1 year following a previous negative FIT. Three-year post-colonoscopy CRC (PCCRC-3yr), which was defined as CRC detected within 3 years after the previous colonoscopy with negative CRC, was also investigated. Differences in the lesion and patient characteristics were compared for patients with the following CRC using the chi-squared test: i) screen-detected and non-screen-detected CRC; ii) (a) FIT-interval cancer, (b) PCCRC-3yr, (c) CRC detected within 1 year after a positive FIT with noncompliance to colonoscopy, and (d) CRC other than (a), (b), and (c).

Results

Of 1,241 CRC patients (1064 with invasive and 177 with intramucosal CRC), 475 (38.3%) had screen-detected and 766 (61.7%) had non-screen-detected CRCs. Non-screen detected CRCs showed significantly higher proportions of presence of ≥T2 invasion, metastasis, worse histology (poorly differentiated adenocarcinoma, signet-ring cell, or mucinous carcinoma) and left-sided CRCs than screen-detected CRC (82.1% vs 52.8% (P<0.01); 52.0% vs 26.7% (P<0.01); 18.7% vs 11.4% (P<0.01); 71.1% vs 61.7% (P<0.01), respectively). FIT-interval cancer (a), PCCRC-3yr (b), and CRC detected within 1 year after a positive FIT with noncompliance to colonoscopy (c) accounted for 4.5%, 7.0%, and 3.9% of all CRCs, respectively, and for 3.9%, 5.4%, and 4.3% of invasive CRCs, respectively. The comparison among these three types (a, b, c) and the other (d) demonstrated a significant difference in the proportions of ≥T2 invasion ((a) 58.9%, (b) 44.8%, (c) 87.5%, and (d) 73.0%, respectively (P<0.01)), metastasis ((a) 33.9%, (b) 21.8%, (c) 54.2%, and (d) 43.9%, respectively (P<0.01)), right-sided CRC ((a) 42.9%, (b) 40.2%, (c) 18.8%, and (d) 28.6%, respectively (P<0.01)), and female patients ((a) 53.6%, (b) 49.4%, (c) 27.1%, and (d) 41.6% respectively (P=0.02)).

Conclusion

Non-screen-detected CRC accounted for a large proportion of patients and demonstrated advanced characteristics in terms of invasion depth and metastasis, as well as CRC detected shortly after a positive FIT with no colonoscopy. These findings emphasize the importance of screening and colonoscopy compliance following a positive FIT. Notably, FIT-interval cancer and PCCRC-3yr existed in non-negligible proportions even under the annual FIT screening system and were characterized by higher proportions of a right-sided location and female. This novel finding suggests that these two types of CRCs may have different biological features from the others.

Introduction

Colorectal cancer (CRC) remains the second most common cause of cancer-related mortality worldwide (1). The introduction of the Danish national CRC screening program in 2014 aimed at reducing mortality rates (2) has marrkedly increased colonoscopies and polypectomies (3,4). A a comprehensive description of the lesions removed has not yet been investigated.

Aims & Methods

Nationwide, cross‑sectional study of all colorectal lesions resected endoscopically in patients ≥18 years between January 2014 and December 2021. Data were obtained from the Danish National Patient Register, Pathology Register and Screening Database. Prevalence of histological sub‑types and predictors of high‑grade dysplasia (HGD) and adenocarcinoma were analyzed with multivariable logistic regression.

Results

Among 663,624 individuals undergoing 1,074,236 colonoscopies or sigmoidoscopies, 194,941 patients (median age 67 years, 58.6% male) had a total of 504,386 lesions removed. Tubular adenomas (TA) accounted for 66.8% of lesions.
The proportion of advanced colorectal polyps—defined as lesions ≥10 mm, adenomas with high-grade dysplasia, or sessile serrated lesions with any dysplasia—declined from 22.7% in 2014 to 10.2% in 2021.
High-grade dysplasia (HGD) was strongly associated with size ≥10 mm (OR 27.1 for 10–19 mm; OR 71.1 for 30–39 mm), and in diminutive lesions (1–5 mm), with tubulovillous or villous histology (OR 6.09).
Adenocarcinoma was identified in 0.65% of lesions and was predominantly left-sided (83.9%), with highest odds observed in the sigmoid colon (OR 6.33) and rectum (OR 6.00), compared to the caecum.
Sex was significantly associated with the risk of adenocarcinoma at the lesion level, but this effect was age-dependent. At age 40, women had significantly higher odds than men (adjusted OR 1.48), but the difference diminished with increasing age, and from age 75 onward, no statistically significant difference between sexes was observed.

Conclusion

Lesion size was the strongest predictor of high-grade dysplasia, outweighing histologic subtype once lesions exceeded 10 mm. At lesion level, the risk of malignancy was higher in younger women than in men of the same age, with the difference progressively diminishing with age. The introduction of the screening programme coincided with a marked reduction in advanced lesions over time. The high predominance of left-sided cancerous lesions highlights the need to optimize the detection of right-sided neoplasia.

References

1. Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, et al. Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J Clin [Internet]. 2021 May 1 ;71(3):209–49. Available from: https://onlinelibrary.wiley.com/doi/full/10.3322/caac.21660
2. Kanth P, Inadomi JM. Screening and prevention of colorectal cancer. BMJ [Internet]. 2021 Sep 15;374. Available from: https://www-bmj-com.ez.statsbiblioteket.dk/content/374/bmj.n1855
3. Adamsen S, Mosbach KKT, Milliam PB, Hansen OH. Injuries by colonoscopy and sigmoidoscopy requiring laparotomy. Claims to the Patient Insurance Corporation. Ugeskr Laeger. 2007 May 7;169(19):1788–93.
4. Baatrup G. Lokal resektion af tidlige kolorektale cancere - og hvad gør vi så?. Ugeskr Laeger. 2021 Jun 28;183(26).

Introduction

Bowel preparation is essential to high quality colonoscopy examination. Whether excellent bowel preparation can increase adenoma detection rate(ADR) comparing with good bowel preparation are still controversial.

Aims & Methods

A prospective, multi-center, observation study was designed to compare ADR between excellent and good bowel preparation based on BBPS in early CRC screening. Subjects aged 40 that received PEG bowel preparation were enrolled. Subject characteristics, bowel preparation quality and colonoscopy data were collected. BBPS score 8-9 was defined as excellent and 6-7 as good. Primary endpoint was ADR. Secondary endpoints included polyp detection rate (PDR), advanced adenoma detection rate (AADR), and the detection rate of different diameter lesions (≤5mm, 6-9mm, ≥10mm).

Results

1503 subjects (aged 40-75, ITT population) from 14 hospitals enrolled, 723 (48.1%) got excellent quality of bowel preparation, 707（47.0%）got good quality of bowel preparation. ADR was significant higher in excellent quality group (35.8% vs 26.9%, P<0.001), especially in trans (13.0% vs 9.6%, P=0.036) and right colon(12.5% vs 8.2%, P=0.008)， numerical higher but no significant difference for left colon（23.5% vs 19.8%，P=0.089）. Excellent quality group had significant higher PDR (57.0% vs 45.1%, P<0.001), especially in left (44.7% vs 35.6%, P<0.001) and trans colon(18.9% vs 14.1%, P=0.015)，numerical higher but no significant difference for right colon（16.0% vs 14.0%，P=0.280）. AADR was also significant higher in excellent quality group (3.2% vs 1.4%, P=0.026) . ≤5mm lesions detection rate was significant higher in excellent quality group (47.6% vs 35.4%, P<0.001), no significant difference for the lesions of 6-9mm/≥10mm. PP set on analysis supported these result. Sex(female 53.9% vs male 47.1%，RR: 1.1, 95%CI[1.0-1.3], P<0.001), risk factors of inadequate bowel preparation (no 60.9% vs yes 42.8%, RR 1.4, 95%CI[1.3-1.6, P<0.001]), bowel preparation regiment (split dose 53.7% vs one dose 46.3%, RR1.1, 95%CI [1.1-1.2], P<0.001), PEG volume( 4L 53.4% vs <4L 46.6%， RR 1.4, 95%CI[1.3-1.6], P<0.001), diet compliance (full compliance 52.2% vs other 44.26%, RR: 1.2, 95%CI[1.0, 1.4], P=0.015) as well as run-away time（2-5hour 53.8% vs other 46.2%, RR: 1.1, 95%CI[1.0, 1.3], P=0.017）were significant associated factors of excellent bowel preparation.
Table1 Lesion Detection Rate Comparing Between Excellent and Good Bowel Preparation (ITT population)

Conclusion

We should seek excellent bowel preparation due to higher ADR, PDR and AADR, especially for ≤5mm lesions. For male and populations with inadequate bowel preparation risk factors, enhance diet education, 4L PEG, split dose and right run-away time could help to get excellent bowel preparation.