Society: ASGE

Background: Post-polypectomy colonoscopy surveillance can reduce the burden of colorectal cancer (CRC). However, the effectiveness of using the faecal immunochemical test (FIT) in the interval between surveillance colonoscopies for the detection of missed or rapidly progressing lesions in individuals at above-average risk of CRC, has not yet been adequately investigated. This study assessed the effectiveness of interval FIT for early detection of advanced neoplasia and the diagnostic accuracy of FIT in above-average risk people who undergo surveillance colonoscopy.

Methods: 7311 individuals from South Australia deemed to be at above-average risk of CRC due to a family history of CRC and/or a personal history of precursor lesions, and who had undergone at least 2 colonoscopy procedures were included. Individuals with a genetic syndrome, inflammatory bowel disease or previous CRC were excluded. A 2-sample FIT (OC Sensor, Eiken Chemical Company) was offered at 1-2 yearly intervals between colonoscopies, where a positive FIT result (≥20 µg Hb/g faeces) triggered an early colonoscopy from the scheduled surveillance time. FITs returned within 3 months before a complete colonoscopy were used to determine the diagnostic accuracy of FIT. Competing-risk regression was used to assess the association between interval FIT result and the risk of having advanced precursor lesions or CRC (advanced neoplasia).

Results: 9737 pairs of colonoscopies were included, with 38,424 years of total analysis time at risk. The mean (SD) age of participants was 62.7 y (±9.7) and 51% were female. Cumulative
FIT positivity was 18.1% (1388/7654). A positive FIT brought forward the time to diagnosis of cancer by 30 months (IQR: 22-38) and diagnosis of advanced precursor lesions by 20 months (IQR: 12-39). Individuals who had returned 4 consecutive negative FIT results had a significantly lower incidence of advanced neoplasia compared to individuals who did not complete a FIT (6.4% vs 10.2%, p<0.001) or individuals returning a positive FIT (6.4% vs 14.1%, p<0.001). The incidence of advanced neoplasia was lowest among those with 4 consecutive negative FIT results (subdistribution hazard ratio (SHR), 0.54; p = 0.001) and highest among those who returned 1 positive FIT (SHR, 2.62; p <0.001). Of the 689 FITs returned within 3 months prior to a complete colonoscopy, the test was positive for 4/6 cancers (sensitivity:66.7%) and 42/157 (sensitivity:26.8%) advanced precursor lesions.

Conclusion: Interval FIT enabled earlier detection of advanced neoplasia in individuals at elevated risk of CRC. Multiple rounds of negative FIT are likely to indicate a lower risk of advanced neoplasia compared to those not participating in interval FIT surveillance. The interval FIT is a significant predictor of advanced neoplasia risk and could be used as a tool to personalise surveillance colonoscopy intervals.

Background: Data about comparative effectiveness of screening with faecal immunochemical test (FIT) and with sigmoidoscopy (FS) are limited
Aims: To compare colorectal (CRC) incidence and mortality at 15-year follow-up among subjects enrolled in the FS and FIT arms in the SCORE2 (1) and SCORE 3 (2) trials.
Methods: Between November 1999 and June 2004, average risk men and women, aged 55 to 64, included in a general population sample, were enrolled in the SCORE2 and SCORE3 trials, aimed to comparative the effectiveness of different CRC screening strategies (fig.1). Invitation and examination procedures were the same in the two trials.
Only subjects randomly invited (by a personal invitation letter) to undergo FIT or FS screening are included in this analysis. Subjects with a negative FS were no longer invited, while those in the FIT arm were invited every 2 years, until age 69. The Immudia-HemSp method (Fujirebio Inc.) was used in the first two rounds of the SCORE2 and in the first round of the SCORE3 trial. All samples were processed in a centralized laboratory. The local programs subsequently adopted the OC Sensor method (Eiken co.), using 20 µg/gr. positivity cut-off. FS was performed by gastroenterologists in hospital endoscopy units. Bowel preparation was limited to a single enema self-administered at home 2 hours before the test. Colonoscopy was recommended if ≥1 polyp ≥10 mm, or ≥1 advanced adenoma, or ≥3 adenomas, or CRC was found at FS.
Follow-up was performed though automated record linkage of the trials database with the local population cancer and mortality registries. Time-to-event data were censored at time of CRC diagnosis (incidence), emigration, death, or 15 years, whichever came first. Outcome measures were CRC incidence and mortality. Adjusted hazard ratios (HR) were estimated using Cox proportional hazard models lumping the groups from the two trials. Individual patient data metanalysis is also planned.
Results: Overall, 23896 subjects were randomized to FS and 11236 to FIT screening. Participation in the initial round was 29% and 32% for FIT and 28% and 32% for FS in the SCORE2 and SCORE3 trials. During the 15-year follow-up at least 1 FIT was performed by 48% of subjects in the FIT arm performed at least 1 FIT (average FIT number=3) and by 46% of responders and 19% of non-responders in the FS arm. CRC incidence was reduced by 15% (HR: 0.85; 95%CI: 0.73-0.99) and mortality was reduced by 17% (HR:0.83; 95%CI:0.59-1.17) in the FS as compared to the FIT arm (fig.2).
Conclusions: CRC incidence was significantly reduced among subjects undergoing FS as compared to those undergoing FIT screening; the CRC mortality reduction did not reach the level of statistical significance. Participation in the FIT arms was lower than in many currently ongoing programs.
1) Segnan et al JNCI 2005 97(5)
2) Segnan et al. Gastroenterology 2007 131(7)

Background: Adenoma detection rate (ADR) is considered the single most important quality measure in colonoscopy. Endocuff-vision is a new generation of single-use, plastic device, mounted on the distal tip of the colonoscope and may potentially improve the visualization of the polyps located behind folds and flexures. However, the performance of Endocuff-vision assisted colonoscopy in Asian endoscopists had never been evaluated.

Method: Patients underwent sedative colonoscopy performed by 13 endoscopists (7 young and 6 seniors [>10 years experiences]) for either symptoms or screening or surveillance were consecutively enrolled between December 2019 and June 2020 and allocated to receive Endocuff-assisted or standard colonoscopy in block randomization. Patients who took antiplatelet, anticoagulants; having history of colectomy or inflammatory bowel disease; poor colon preparation or scheduled for endoscopic treatment were excluded. Primary outcome of study was ADR; Secondary outcomes included polyp detection rate (PDR), advanced ADR, adenomas per colonoscopy (APC), sessile serrated lesion detection rate (SDR), cecal intubation time, withdrawal time and adverse events.

Results: A total of 1,212 patients were screened for eligibility and finally 1,016 patients (median age of 56 years, 47.3% male) were included for analysis. Among them, a total of 553 patients (54.4%) received endocuff-assisted and 463 standard colonoscopies. The ADR (39.2% vs. 32.2%; P = 0.02), PDR (55.5% vs. 47.1%; P = 0.007) and APC (0.8 ± 1.3 vs. 0.6 ± 1.1; P =0.029) were significantly higher in the endocuff group than those in the standard group (Table 1). Endocoff was associated with a shorter cecal intubation time (4.2 ± 3.8 vs. 4.9 ± 4.0 minutes; P = 0.004). The differences in ADR (37.3% vs. 27.5%; P = 0.036) and cecal intubation time (5.0 ± 3.3 vs. 6.5 ± 4.6 minutes; P < 0.001) were larger, when performed by young endoscopists (Table 2). Minor mucosal laceration was found in 3 patients, and no serious adverse events reported.

Conclusion: New-generation Endocuff-assisted colonoscopy may not only improve the ADR, PDR and APC, but also shorten the cecal intubation time, especially in young endoscopists. Endocuff-vision can be routinely used to improve the quality and performance of colonoscopy.

Background and Aims:
Increasing adenoma detection rate (ADR) could be beneficial in reducing the risk of post-colonoscopy colorectal cancer. Texture and Color Enhancement Imaging (TXI) and Endocuff Vision (ECV) are found to improve ADR. TXI improves polyp detection by enhancing endoscopic images’ brightness and color contrast while maintaining color appearance close to white light imaging. Due to our impressive experience with TXI and the current evidence, our center uses TXI during inspection as a standard. Endocuff Vision (ECV) is a mucosal exposure device that helps flatten the colonic folds and increases ADR. The combined benefit of TXI and ECV have not been studied before; thus, this study aimed to compare the ADR between the combined TXI with ECV and TXI alone.

Methods:
We conducted a prospective randomized controlled trial recruiting patients age ≥40 years who undergo colonoscopy for colorectal cancer screening or any gastrointestinal symptoms. The participants were enrolled and randomized in a 1:1 ratio into TXI with ECV group (TXI+ECV group) and TXI group. Experienced endoscopists with ≥40% ADR performed all colonoscopies. Data on baseline characteristics, bowel preparation quality, intubation time, withdrawal time, and polyp characteristics were collected. Primary outcome was ADR. Secondary outcomes were adenoma per colonoscopy (APC), serrated lesion detection rate (SLDR), insertion time, and withdrawal time.

Results:
Four hundred patients were included in this study. Nineteen patients were excluded after randomization due to poor bowel preparation, colorectal cancer, colonic stricture, and failure to reach the cecum. Finally, there were 189 patients in the TXI+ECV group and 192 in the TXI group (Figure 1). Baseline characteristics between the two groups were comparable. The ADR was significantly higher in the TXI+ECV group than in the TXI group (65.6% vs. 52.1%, p=0.007). The APC was significantly greater in the TXI+ECV group than in the TXI group (1.6 vs. 1.2, p=0.021), prominently proximal (1.0 vs. 0.7, p=0.031), non-pedunculated (1.4 vs. 1.1, p=0.035), and diminutive (1.3 vs. 1, p=0.045) adenomas (Table 1). The SLDR, insertion time, and withdrawal time were not different between the two groups.

Conclusions:
Our study found that adding ECV to TXI significantly improves ADR and APC compared with TXI alone.

Trial registration: Thai Clinical Trials Registry TCTR20220507004

Background & Aims: Sessile serrated lesions (SSL) are associated with increased risk of colorectal cancer (CRC). Prevalence of SSL in Asia and its’ related factors remained poorly studied. We performed this study to estimate the prevalence of SSL in Asia and to evaluate possible clinical predictors of SSL.
Methods: This is a post-hoc analysis on a cohort of patients who underwent colonoscopy from November 2020 to January 2022 as part of ATLAS trial, which was a multicenter parallel arm RCT involving 11 centers across 4 countries/regions in Asia comparing the adenoma detection rate between linked-color imaging (LCI) and white light imaging (WLI). Patients were at average risk of CRC and underwent colonoscopy as part of diagnostic workup, screening or surveillance colonoscopy. Demographics, procedure related information including indication of colonoscopy, previous history of polypectomy and endoscopic findings were recorded in a central database. All histopathological slides were reviewed by dedicated gastrointestinal pathologists from each institution. We report the estimated prevalence of SSL. Patients with SSL were compared against those without SSL to evaluate for possible predictors of SSL.
Results: A total of 3050 participants were enrolled and included in the final analysis. The estimated prevalence of SSL was 3.8% (95% CI 3.2 to 4.6) against 52.7% (95% CI 50.9 to 54.5) for adenomas. Patient demographics and procedure related characteristics in the two groups are shown Table 1. The withdrawal time and quality of bowel preparation between the two groups were similar. Based on univariable analyses, a presence of adenoma (OR 2.55, 95% CI 1.68 to 3.86, p<0.001), advanced adenoma (OR 2.19, 95% CI 1.40 to 3.43, p = 0.001) and previous history of polypectomy (OR 1.74, 95% CI 1.20 to 2.53, p=0.004) were associated with increased detection of SSL. In addition, colonoscopy by expert endoscopists (OR 1.88, 95% CI 1.24 to 2.83, p=0.003), Use of LCI (OR 1.74, 95% CI 1.19 to 2.55, P=0.004), and transparent cap (OR 1.96, 95% CI 1.30 to 2.97, p=0.001) were associated with higher rate of detection of SSL. On multivariable analyses using Firth’s logistic regression (Table 2), a presence of adenoma, previous history of polypectomy, endoscopy by expert endoscopists, use of LCI, and transparent cap remained statistically significant predictors of SSL with OR of 2.18 (95% CI 1.39 to 3.43, p=0.001), OR 1.66 (95% CI 1.01 to 2.73, p=0.046), OR 1.57 (95% CI 1.03 to 2.40, p=0.035), OR 1.62 (95% CI 1.10 to 2.38, p=0.015), and OR 1.67 (95% CI 1.08 to 2.58, p=0.020) respectively. Age and gender were not predictive of SSL.
Conclusion: Current and previous adenoma/polyp detection, expert endoscopists, LCI and use of transparent cap are associated with increased detection of SSL. The reported prevalence of SSL in Asia may be under-estimated due to endoscopy-related factors.

Table 1 Participants’ demographics and procedure related characteristics

Table 1 Participants’ demographics and procedure related characteristics

Table 2 Univariate analysis and multivariate logistic regression of factors associated SSL

Table 2 Univariate analysis and multivariate logistic regression of factors associated SSL

Background and aims:
Non-granular (NG) large (>20mm) non-pedunculated colorectal polyps (LNPCPs) are a distinct entity in colorectal neoplasia, with a reported increased risk of submucosal invasive cancer (SMIC). Increasing LNPCP size, nodular or depressed morphology and left colon location are well-defined risk factors for SMIC in LNPCPs. It is currently unknown if NG-LNPCPs conform to this model or demonstrate their own unique features.

Methods:
All patients referred for resection of LNPCPs over 138 months until November 2022 were enrolled. Serrated lesions were excluded from analysis. All cases of LNPCPs with SMIC were identified from endoscopic resection specimens, lesion biopsies, or surgical histopathology. The study aim was to identify the dominant characteristics of NG-LNPCPs containing SMIC.

Results:
2442 lesions were eligible for final analysis. Median LNPCP size was 35mm (IQR 25-50mm) with 1452 (59.5%) located in the right colon and a predominant Paris 0-IIa (1284 (52.6%)), granular (1600 (65.5%)) morphology . 286/2442 (11.7%) cancers were identified with 208/286 (73%) treated endoscopically. After adjustment for lesion size, location, and morphology, NG-LNPCP were more likely to harbour SMIC (OR 2.85; 95% CI 2.12-3.83, p<0.001). Compared to granular LNPCPs (G-LNPCPs), NG-LNPCPs containing SMIC are less likely to be >40mm in size (OR 0.46; 95%CI 0.27-0.80, p=0.006) or sessile morphology (OR 0.22; 95%CI 0.12-0.38, p<0.001) and more likely to be in the right colon (OR 1.87; 95%CI 1.07-3.26, p=0.03).

Conclusion:
NG-LNPCPs containing SMIC differ to G-LNPCPs, being smaller, right-sided, flat lesions. These subtle lesions, demonstrate an aggressive pathway to carcinogenesis and must be carefully detected and resected by colonoscopists.

Background/Aims:
Sessile serrated lesions (SSLs) have the malignant potential for colorectal cancer in the serrated pathway. Selective endoscopic resection of SSLs would reduce medical costs and procedure-related accidents, but the accurate endoscopic differentiation of SSLs from hyperplastic polyps (HPs) is challenging. To explore the differential diagnostic performance of magnifying colonoscopy in distinguishing SSLs from HPs, we conducted a multicenter prospective validation study in clinical practice.
Methods:
Considering the rarity of diminutive SSLs, all lesions ≥6 mm that were detected during colonoscopy and diagnosed as type 1 based on the Japan narrow-band imaging expert team (JNET) classification were included in this study. Twenty expert endoscopists were asked to differentiate between SSLs and HPs with high or low confidence level after conventional and magnifying NBI observation. To examine the validity of selective endoscopic resection of SSLs using magnifying colonoscopy in clinical practice, we calculated the sensitivity of endoscopic diagnosis of SSLs with histopathological findings as a comparable reference.
In addition, the appearance ratio of the eight characteristic findings in the SSL and HP groups was calculated. Furthermore, multivariate logistic regression analysis was performed to determine the usefulness of the eight characteristic findings (irregular shape, indistinct border, cloud-like surface, mucus cap, rim of debris, dilated vessels, dilated crypts, inverted growth pattern) in the differential diagnosis of SSL.
Results:
In four institutions, 4,397 patients who underwent colonoscopies were recruited between December 2019 and October 2020. Among them, 217 JNET type 1 lesions from 162 patients were analyzed, and 114 lesions were diagnosed with high confidence. The sensitivity of magnifying colonoscopy in detecting SSLs was 79.8% (95% confidence interval (CI): 74.7–84.4%) overall, and 82.4% (95% CI: 76.1–87.7%) in the high-confidence group. The mean number of the eight endoscopic findings recognized in the SSL and HP groups was 2.76 and 1.52, respectively. The appearance rates of the eight findings in the SSL vs. HP groups were: irregular shape 41.9% vs. 23.9%, indistinct border 38.0% vs. 20.5%, cloud-like surface 20.9% vs. 8.0%, mucus cap 62.0% vs. 33.0%, rim of debris 16.3% vs. 9.1%, dilated vessels 51.9% vs. 34.1%, dilated crypts 44.2% vs. 20.5%, and inverted growth pattern 0.78% vs. 3.4%. Multivariate logistic regression analysis showed only two findings, mucus cap and dilated vessels, were statistically significant.
Conclusions:
Accurate differential diagnosis of SSLs and HPs using magnifying colonoscopy was challenging even for experts. JNET type 1 lesions ≥6 mm are recommended to be resected because selective endoscopic resection has the disadvantage of leaving approximately 20% of SSLs on site.

Mikio Fujita

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