Introduction

Endoscopic submucosal dissection (ESD) is increasingly promoted as the optimal treatment strategy for all large non-pedunculated colorectal polyps (LNPCP). The effect of a universal en bloc strategy on oncological outcomes for the treatment of LNPCP in the right colon is unknown. We evaluated this in a large Western population.

Aims & Methods

We retrospectively analysed prospectively collected data from major tertiary centres where patients were referred for endoscopic resection (ER) of LNPCP (N=5084). Patients found to have cancer after ER and those referred directly to surgery were included. The primary outcome was to determine the proportion of right colon LNPCP with low-risk cancer.

Results

Over 180 months until June 2023, 3294 sporadic right colon LNPCP in 2956 patients were referred for ER at 7 sites (median size 30mm [IQR 15]). 63 (2.1%) patients were referred directly to surgery and cancer was proven in 56 (88.9%). 2851/2956 (96.4%) LNPCP underwent ER (median size 35mm [IQR 20]) of which 75 (2.6%) were cancers. The overall prevalence of cancer in the right colon was 4.4% (131/2956). Detailed histopathological analysis was possible in 115/131 (88%) cancers (71 after ER, 44 direct to surgery, Table 1). 23/2940 (0.78%) sporadic right colon LNPCP were low-risk cancers.

Table 1: Final Oncologic Outcomes; comparison between histopathologic variables of cases referred directly to surgery versus following endoscopic resection

Conclusion

The proportion of right colon LNPCP referred for ER containing low-risk cancer amenable to endoscopic cure was <1%, in a large, multicentre Western cohort. A universal ESD strategy for the management of right colon LNPCP is unlikely to yield improved patient outcomes given the minimal impact on oncological outcomes, significant resource demands and increased adverse events.

Introduction

EMR is the standard of care for the management of large (≥20mm) non-pedunculated colonic polyps (LNPCPs). However, its efficacy and cost effectiveness, are limited by recurrence and the necessity for scheduled surveillance. Consequently, current surveillance intervals are conservative. Margin thermal ablation (MTA) after EMR for LNPCPs has dramatically reduced the incidence of recurrence at first surveillance colonoscopy at six-months (SC1). If this effect is durable, then subsequent surveillance intervals in patients who have been cleared of synchronous polyps could be substantially lengthened. We prospectively evaluated long-term surveillance outcomes in a cohort of LNPCPs that have undergone MTA.

Aims & Methods

Consecutive patients with LNPCPs undergoing EMR and MTA from four academic endoscopy centres were prospectively recruited. All patients that underwent successful endoscopic resection received SC1 six months post resection. EMR scars were carefully evaluated with high-definition white light, narrow band imaging with near focus and biopsy. In the absence of recurrence, second surveillance (SC2) colonoscopy was conducted at a subsequent interval of 12 months with the scar evaluation process repeated. The primary outcome was recurrence at SC2 in all LNPCPs with a recurrence-free scar at SC1.

Results

1324 LNPCPs referred for EMR were enrolled over 90 months until October 2022. Following exclusions, 1163 LNPCPs underwent EMR with complete MTA. 856 LNPCPs underwent SC1. 32 additional synchronous LNPCPs were cleared at this procedure. 25/856 (2.9%) (95%CI 1.9-4.3%) LNPCPs demonstrated recurrence. 469 LNPCPs free of recurrence at SC1 (median size 35mm) underwent SC2 at a mean interval of 22.9 months (95%CI 21.9-23.95) after the index EMR. 468 demonstrated a bland scar without recurrence. Only one recurrence occurred (0.2% 95%CI 0-1.2%), related to a 0-IIa+Is 20mm granular TVA located on the ileocaecal valve.

Conclusion

LNPCPs that have undergone successful EMR with MTA and are free of recurrence at SC1 are very unlikely to develop recurrence in subsequent surveillance out to 2 years. Following EMR of LNPCPs with MTA, patients who are cleared of synchronous neoplasia and demonstrate no recurrence after careful scar examination, can potentially undergo next surveillance in 3-5 years. Such an approach would reduce costs and enhance patient compliance.

Disclosure

Michael Bourke: Research Support: Olympus Medical, Cook Medical, Boston Scientific
The remaining authors have no financial, professional, or personal conflicts of interest to disclose

Introduction

Endoscopic mucosal resection (EMR) is standard of care for the management of large (≥20mm) non-pedunculated colonic polyps (LNPCPs). Its efficacy and cost effectiveness were limited by recurrence. Margin thermal ablation (MTA) to the post-EMR defect, has greatly mitigated this problem. However, electrocautery-related complications of delayed bleeding and perforation incur significant morbidity.
Cold snare polypectomy is effective and safe for the resection of small polyps with negligible recurrence rates. Application of cold snare resection to LNPCPs, while an attractive alternative, lacks high-quality evidence. We conducted a randomized trial to compare the efficacy and safety of cold EMR (C-EMR) to conventional (H-EMR).

Aims & Methods

A prospective single-centre randomized controlled trial was conducted at an Australian tertiary referral centre for flat, 15-50mm adenomatous LNPCPs referred for endoscopic resection. Prior to resection, eligible LNPCPs were randomly assigned to EMR using a dedicated cold snare or conventional H-EMR with margin thermal ablation (control). First surveillance colonoscopy (SC1) was conducted 6 months following resection. Scars were evaluated with high-definition white-light, narrow-band imaging and biopsy. The primary outcome was endoscopically visible and/or histologically confirmed recurrence at SC1. Secondary outcomes were clinically significant post-EMR bleeding (CSPEB), delayed perforation and technical success.

Results

931 LNPCPs were referred for endoscopic resection between November 2019-September 2023. 177 LNPCPs in 177 patients were randomized to either the C-EMR arm (n=87) or H-EMR arm (n=90). Treatment groups were equivalent with no significant difference in lesion size or technical success (86/87 (98.9%) vs 90/90 (100%); p=0.31). One C-EMR required conversion to H-EMR due to unexpected submucosal fibrosis. Following exclusions, 146 LNPCPs undertook SC1 (76 C-EMR, 70 H-EMR). 5 patients await surveillance. On intention to treat and per protocol analysis, recurrence was significantly greater in C-EMR (16/87, 18.4% vs 1/90, 1.1%; p<0.001 and 16/76, 21.1% vs 1/70, 1.4%; p<0.001 respectively). Significant deep mural injury (27/90 (30%) vs 0; p<0.001) and delayed perforation (1/90 (1.1%) vs 0; p=0.32) only occurred in the H-EMR group. CSPEB and intraprocedural bleeding were significantly greater in the H-EMR arm (7/90 (7.8%) vs 1/87 (1.1%); p = 0.034 and 12/90 (13.3%) vs C-EMR arm 1/87 (1.1%); p=0.002 respectively).

Conclusion

Compared to conventional H-EMR, C-EMR for flat, adenomatous LNPCPs, demonstrates superior safety with equivalent technical success. However, endoscopic recurrence is significantly greater for cold snare resection and is currently a limitation of the technique.

Disclosure

Michael Bourke: Research Support: Olympus Medical, Cook Medical, Boston Scientific
The remaining authors have no financial, professional, or personal conflicts of interest to disclose

Introduction

Post-Faecal Immunochemical Test (FIT) colonoscopy represents a setting with an enriched prevalence of advanced adenomas, mostly due to distal pedunculated polyps. Due to an expected higher risk of Colorectal Cancer (CRC), post-polypectomy surveillance is recommended, generating a substantial overload on endoscopy services. The aim of our study was to investigate the post-polypectomy CRC incidence risk in a screening population of FIT+ subjects after resection of low- (LRA) or high-risk adenomas (HRA).

Aims & Methods

We retrieved data from a cohort of patients undergoing post-polypectomy surveillance within a FIT-based CRC screening program in Italy between 2002 and 2017 followed-up to December 2021. Main outcomes were post-polypectomy CRC incidence and mortality risks according to type of adenoma (LRA/HRA) removed at colonoscopy as well as morphology, size, dysplasia and location of the index lesion. We adopted FIT- subjects as comparators. The absolute risk was calculated as the number of incident CRCs per 100,000 person-years of follow-up. We used Cox multivariable regression models to identify associations between CRC risks and patient- and polyp-related variables.

Results

Overall, we included 87,248 post-FIT+ colonoscopies (133 endoscopists). Of these, 42,899 (49.2%) were negative, 21,650 (24.8%) had a LRA and 22,709 (26.0%) a HRA. After a median follow-up of 7.25 years, a total of 635 CRCs were observed. For patients with LRAs, CRC incidence (Hazard Ratio [HR] 1.15, 95% Confidence Interval [CI] 0.93-1.42) risks were not increased compared to the FIT-negative group, while for HRAs a significant increase in CRC incidence (HR 1.49, 95% CI 1.20-1.86) risks were found. The presence of one or more risk factors among proximal location, non-pedunculated morphology and high-grade dysplasia explained most of this excess CRC risk in the HRA group (HR 1.75, 95% CI 1.37-2.25). Patients with only distal pedunculated polyps without HGD, representing 39.2% of HRA, did not show any increased risk compared to the FIT-negative group (HR 0.84, 95% CI 0.60 - 1.17).

Conclusion

CRC incidence is significantly higher in patients with high-risk adenomas diagnosed at colonoscopy. However, such excess risk does not apply to patients with only distal pedunculated polyps without HGD, substantially reducing the burden of surveillance in FIT programs.

Disclosure

no COI

Introduction

Large non-pedunculated colorectal polyps (LNPCP's) are significant precursors of colorectal cancer, commonly treated by piecemeal endoscopic mucosal resection (pEMR). When histology reveals a focus of adenocarcinoma invading the sub-mucosa, the resection is often considered non curative and salvage surgery is performed. Recent evidence shows that the risk of residual cancer in the bowel wall or lymph nodes of the surgical specimen are uncommon and that in some cases surgery may be avoided even when a focus of invasive cancer is found in the EMR specimen.

Aims & Methods

This is a retrospective observational study aimed to evaluate the prevalence, characteristics, and outcomes of covert carcinoma in LNPCPs resected by EMR in a two academic centers.
Data was collected from a prospective cohort of LNPCPs at two academic centers in Israel. We collected patient, lesion and procedural characteristics prospectively.
EMR was performed by 3 experienced endoscopist with dedicated EMR training. Piecemeal EMR was performed after endoscopic assessment for polyps that were deemed not to have sub-mucosal invasion according to accepted classification systems. Lesions suspected to containing invasive cancer were referred to surgery without endoscopic resection were excluded from the analysis.
For lesions containing invasive carcinoma, data was collected on Kikuchi classification, presence of tumor budding and lymphovascular invasion, grade of tumor differentiation, and status of the deep margin. Surgical data included presence of residual carcinoma in the surgical specimen, grading, margin involvement, and lymph node involvement.

Results

We analyzed 546 LNPCPs referred for resection at the two centers. We identified 27 cases of covert carcinoma, accounting for 4.9% of all LNPCPS resected by piecemeal EMR. A multidisciplinary tumor board deemed resection curative in 7 cases, and 18 patients were refferd for surgical resection. One patient refused surgery, and One patient was lost to follow up.
None of the surgical specimens had lymph node metastasis. In one case residual carcinoma was found in the bowel wall of the surgical specimen. No recurrence of colorectal cancer, presence of metastasis on imaging or elevation of CEA was documented for any of the patients during follow up of two year.

Conclusion

In conclusion, our study shows that covert carcinoma is relatively rare when EMR is performed in a high-volume center by expert endoscopists. In addition, the data suggests that even in these cases, the risk of metastatic disease is probably very low.

References

1. Kudo S ei, Lambert R, Allen JI, Fujii H, Fujii T, Kashida H, et al. Nonpolypoid neoplastic lesions of the colorectal mucosa. Gastrointest Endosc. 2008 Oct;68(4 SUPPL.).
2. Ferlitsch M, Moss A, Hassan C, Bhandari P, Dumonceau JM, Paspatis G, et al. Colorectal polypectomy and endoscopic mucosal resection (EMR): European Society of Gastrointestinal Endoscopy (ESGE) Clinical Guideline. Vol. 49, Endoscopy. Georg Thieme Verlag; 2017. p. 270–97.
3. Lopez A, Bouvier AM, Jooste V, Cottet V, Romain G, Faivre J, et al. Outcomes following polypectomy for malignant colorectal polyps are similar to those following surgery in the general population. Gut. 2019 Jan 1;68(1):111–7.
4. Choi YS, Kim WS, Hwang SW, Park SH, Yang DH, Ye BD, et al. Clinical outcomes of submucosal colorectal cancer diagnosed after endoscopic resection: A focus on the need for surgery. Intest Res. 2020 Jan 1;18(1):96–106.
5. Gibson DJ, Sidhu M, Zanati S, Tate DJ, Mangira D, Moss A, et al. Oncological outcomes after piecemeal endoscopic mucosal resection of large non-pedunculated colorectal polyps with covert submucosal invasive cancer. Gut. 2022 Mar 7;

Disclosure

Conflicts of interest: None. Financial disclosures: None.

Introduction

The JNET (Japan NBI Expert Team) classification can be used to predict large non-pedunculated colorectal polyp (LNPCP) histology and presence/depth of submucosal invasion (SMI). Japanese endoscopist accuracies >84% have not been replicated in the West; for example, in a recent study of European experts the accuracy of JNET was 55%.  Furthermore, European guidelines suggest both low-grade dysplasia (LGD) and high-grade dysplasia (HGD) can be treated using endoscopic mucosal resection (EMR) thus there is no clinical consequence to interpreting HGD as JNET 2A (excluded in the original interpretation of JNET).

Aims & Methods

We aimed to validate a novel tool CRIS (Colorectal Regular-Irregular Score) by comparing it with JNET for LNPCP histology prediction amongst Western experts.
32 images of flat LNPCPs under narrow-band imaging were consecutively obtained with matching histopathology data. Each image was rated (anonymous online survey) using JNET and then all the images were rated again (order randomised) using CRIS, a tool which simply asks whether the most disordered vascular pattern visible in the image is ‘regular(=CRIS-R), regularly-irregular(=CRIS-RI) or completely-irregular(=CRIS-I)’. No further explanation of JNET or CRIS was offered. Accuracy of JNET and CRIS vs. histopathology was analysed using the original JNET interpretation (where JNET 1/2A and CRIS-R = LGD) and a clinically relevant approach (where JNET1/2A and CRIS-R can also = HGD). JNET2B & CRIS-RI were matched to HGD & superficial SMI and JNET3 & CRIS-I to deep SMI. Correct treatment was defined as pEMR for LGD or HGD, en-bloc EMR/ESD for HGD or superficial SMI and surgery for deep SMI.

Results

12 experts (median 150 colorectal EMRs and 13 ESDs/year) rated 32 images.
The overall accuracy of JNET vs. histopathology using the original JNET interpretation was 69.7% (95%CI) 46.0-89.3%] and CRIS 69.6% (95%CI 45.3-88.7%). Expert agreement was similar between JNET (91.3% (95%CI) 82.8-98.3%) and CRIS (88.5% [95%CI 78.2-97.3%]) with Κ=0.64 (moderate) for JNET and Κ=0.57 (moderate) for CRIS.
The accuracy of JNET 2B was 51.7% (95%CI 45.9-57.4%) and JNET 3 85.8% (95%CI 81.2-89.3%). Comparably CRIS-RI and CRIS-I showed accuracies of 51% (95%CI 45.2-56.7%) and 85.1% (95%CI 80.4-88.7%) respectively.  Correct treatment was determined in 144/288 (50.0%) observations using JNET and 144 (50.0%) using CRIS. Using the clinically relevant approach the accuracy of JNET was 73.9% (95%CI 46.0-89.3%) vs. CRIS 72.3% (95%CI 45.3-88.7%).
The accuracy, sensitivity and specificity of JNET 1/2A changed by +13.2%, -8.0% and +38.0% and CRIS-R by 8.3%, -8.2% and 35.5%. Correct treatment determination increased by 29.5% to 79.5% for JNET and by 27.1% to 77.1% for CRIS. 

Conclusion

Both JNET and CRIS, a novel score named and described by 3 self-explanatory words, can be used by Western experts to accurately determine LNPCP histology.This suggests JNET may be able to be simplified for non-experts. Importantly the accuracy of both JNET and CRIS can be increased by framing their interpretation versus. histology in a clinically relevant fashion. This has significant implications for signposting patients to correct treatment after detection of LNPCPs especially amongst non-experts.

References

• Ferlitsch M, et al. Colorectal polypectomy and endoscopic mucosal resection (EMR): European Society of Gastrointestinal Endoscopy (ESGE) Guideline (update 2024). In press.
  
• Kobayashi S, Yamada M, Takamaru H, et al. Diagnostic yield of the Japan NBI Expert Team (JNET) classification for endoscopic diagnosis of superficial colorectal neoplasms in a large-scale clinical practice database. United European Gastroenterol J. 2019;7(7):914-923. doi:10.1177/2050640619845987 
• Sano Y, Tanaka S, Kudo SE, et al. Narrow-band imaging (NBI) magnifying endoscopic classification of colorectal tumors proposed by the Japan NBI Expert Team. Dig Endosc 2016; 28: 526–533. 
• Saito Y, Sakamoto T, Dekker E, Pioche M, Probst A, Ponchon T, Messmann H, Dinis-Ribeiro M, Matsuda T, Ikematsu H, Saito S, Wada Y, Oka S, Sano Y, Fujishiro M, Murakami Y, Ishikawa H, Inoue H, Tanaka S, Tajiri H; IEE-JNET Group. First report from the International Evaluation of Endoscopic classification Japan NBI Expert Team: International multicenter web trial. Dig Endosc. 2023 Sep 13. doi: 10.1111/den.14682. Epub ahead of print. PMID: 37702082. 

Disclosure

DJT: Research support and consulting from Olympus, Pentax and Fujifilm.