Large non-pedunculated colorectal polyp management: The elephant in the room.

Minimally invasive innovations have transformed coloproctology. Specific to colorectal cancer (CRC), there has been a shift towards less invasive surgical techniques and use of endoscopic resection as an alternative for low risk T1 CRC. The role of endoscopic resection is however much more extensive: It is now considered the first line management strategy for most large (≥ 20 mm) non-pedunculated colorectal polyps, the majority of which are benign. This is due to the well-established efficacy, safety, and cost-effectiveness of endoscopic techniques compared to surgery. Multiple endoscopic modalities now exist with distinct risk-benefit profiles and their outcomes are further improved by site-specific technical modifications, auxiliary techniques, and adverse event mitigation strategies. Endoscopic capacity continues to evolve with emerging endoscopic techniques and expanding applications, particularly in the confines of a multi-disciplinary setting.

Double-nylon purse-string suture technique: Another addition to the endoscopist's toolbox for full-thickness defect closure.

Iatrogenic perforation is the most feared adverse event in endoscopy. With the expansion of interventional endoscopy in favor of traditional surgery, it is now more crucial than ever to develop effective defect closure techniques. This has culminated in the dissemination of multiple novel closure technologies, including through-the-scope clips, over-the-scope clips, through-the-scope suturing and over-the-scope suturing devices. In this editorial, we comment on the recent publication by Wang and colleagues discussing the performance of the double-nylon purse-string suture technique in the closure of large (> 3 cm) gastric full-thickness defects. This technique offers a promising, practical and cost-effective approach to closure of large full-thickness defects that can be readily implemented across diverse healthcare settings.

T1 colorectal cancer management in the era of minimally invasive endoscopic resection.

T1 colorectal cancer (CRC), defined by tumor invasion confined to the submucosa, has historically been managed by surgery. Improved understanding of recurrence and lymph node metastases risk, coupled with advances in endoscopic resection techniques, have led to an increasing capacity for organ-sparing local excision. Minimally invasive management of T1 CRC begins with optical evaluation of the lesion to diagnose invasive disease and quantify depth of invasion, which informs therapeutic decision making. Modality selection between various available endoscopic resection techniques depends upon lesion characteristics, technique risk-benefit profiles, and location-specific implications. Following endoscopic resection, established histopathology features determine the risk of recurrence and subsequent management including surveillance or adjuvant surgical excision. The management of non-operative candidates deviates from conventional recommendations with emerging treatment strategies in select populations.

Peroral endoscopic myotomy in the presence of small esophageal varices.

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Endohepatology: Arrival at the frontier of interventional endosonography.

Endohepatology describes the emerging field where diagnostic and therapeutic endoscopic ultrasound (EUS) are used for the diagnosis and management of liver disease and its sequelae. In this editorial we comment on the article by Gadour et al. The spectrum of EUS-guided procedures includes liver parenchymal and lesional biopsy, abscess drainage, treatment of focal liver lesions, diagnosis of portal hypertension and management of gastric varices. The data suggest that the application of EUS to hepatology is technically feasible and safe, heralding the arrival at a new frontier for EUS. More data, specifically randomised trials comparing EUS to interventional radiology techniques, and continued partnership between endoscopy and hepatology are required to see this field establish itself outside expert tertiary centres.

Incomplete Mucosal Layer Excision during Endoscopic Mucosal Resection: a potential source of recurrent adenoma.

BACKGROUND AND AIMS: Residual or recurrent adenoma detected during surveillance (RRA) is the major limitation of endoscopic mucosal resection (EMR). The pathogenesis of RRA is unknown although thermal ablation of the post-EMR defect (PED) margin reduces RRA. We aimed to identify a feature within the PED which could be associated with RRA. METHODS: Between 1/2017 and 7/2020 detailed prospective procedural data on all EMR procedures performed at a single centre were retrospectively analysed. At the completion of EMR the PED was systematically examined for features of incomplete mucosal layer excision (IME). This was defined as a demarcated area within the PED bordered by a white electrocautery ring, containing endoscopically identifiable features suggesting incomplete resection of the mucosa including lacy capillaries and/or visible fibres of the muscularis mucosae. Areas of IME were re-injected and re-excised by snare and submitted separately for blinded specialist gastrointestinal pathologist review. RESULTS: EMR was performed for 508 large non-pedunculated colorectal polyps (LNPCPs) (median size 35mm). In 10 PED (2.0%) an area of IME was identified and excised. Histopathological examination of areas of suspected IME demonstrated muscularis mucosae in 9/10 (90%), residual lamina propria in 9/10 (90.0%) and residual adenoma in 5/10 (50.0%). No RRA was detected during follow-up after re-excision of IME. CONCLUSION: We report the novel finding of IME within the PED after EMR of LNPCPs. IME may contain microscopic residual adenoma and therefore is a risk for RRA during follow-up. After completion of EMR the PED should be carefully evaluated and if IME is found it should be excised.

Safety and efficacy of physician-administered balanced-sedation for the endoscopic mucosal resection of large non-pedunculated colorectal polyps.

Background and study aims Because of concerns about peri-procedural adverse events (AEs), guidelines recommend anesthetist-managed sedation (AMS) for long and complex endoscopic procedures. The safety and efficacy of physician-administered balanced sedation (PA-BS) for endoscopic mucosal resection (EMR) of large non-pedunculated colorectal polyps (LNPCPs) ≥20 mm is unknown. Patients and methods We compared PA-BS with AMS in a retrospective study of prospectively collected data from consecutive patients referred for management of LNPCPs (NCT01368289; NCT02000141). A per-patient propensity analysis was performed following a 1:2 nearest-neighbor (Greedy-type) match, based on age, gender, Charlson comorbidity index, and lesion size. The primary outcome was any peri-procedural AE, which included hypotension, hypertension, tachycardia, bradycardia, hypoxia, and new arrhythmia. Secondary outcomes were unplanned admissions, 28-day re-presentation, technical success, and recurrence. Results Between January 2016 and June 2020, 700 patients underwent EMR for LNPCPs, of whom 638 received PA-BS. Among them, the median age was 70 years (interquartile range [IQR] 62-76 years), size 35 mm (IQR 25-45 mm), and duration 35 minutes (IQR 25-60 minutes). Peri-procedural AEs occurred in 149 (23.4%), most commonly bradycardia (116; 18.2%). Only five (0.8%) required an unplanned sedation-related admission due to AEs (2 hypotension, 1 arrhythmia, 1 bradycardia, 1 hypoxia), with a median inpatient stay of 1 day (IQR 1-3 days). After propensity-score matching, there were no differences between PA-BS and AMS in peri-procedural AEs, unplanned admissions, 28-day re-presentation rates, technical success or recurrence. Conclusions Physician-administered balanced sedation for the EMR of LNPCPs is safe. Peri-procedural AEs are infrequent, transient, rarely require admission (<1%), and are experienced in similar frequencies to those receiving anesthetist-managed sedation.

Treatment of adenoma recurrence after endoscopic mucosal resection.

OBJECTIVE: Residual or recurrent adenoma (RRA) after endoscopic mucosal resection (EMR) of large non-pedunculated colorectal polyps (LNPCPs) of ≥20 mm is a major limitation. Data on outcomes of the endoscopic treatment of recurrence are scarce, and no evidence-based standard exists. We investigated the efficacy of endoscopic retreatment over time in a large prospective cohort. DESIGN: Over 139 months, detailed morphological and histological data on consecutive RRA detected after EMR for single LNPCPs at one tertiary endoscopy centre were prospectively recorded during structured surveillance colonoscopy. Endoscopic retreatment was performed on cases with evidence of RRA and was performed predominantly using hot snare resection, cold avulsion forceps with adjuvant snare tip soft coagulation or a combination of the two. RESULTS: 213 (14.6%) patients had RRA (168 (78.9%) at first surveillance and 45 (21.1%) thereafter). RRA was commonly 2.5-5.0 mm (48.0%) and unifocal (78.7%). Of 202 (94.8%) cases which had macroscopic evidence of RRA, 194 (96.0%) underwent successful endoscopic therapy and 161 (83.4%) had a subsequent follow-up colonoscopy. Of the latter, endoscopic therapy of recurrence was successful in 149 (92.5%) of 161 in the per-protocol analysis, and 149 (73.8%) of 202 in the intention-to-treat analysis, with a mean of 1.15 (SD 0.36) retreatment sessions. No adverse events were directly attributable to endoscopic therapy. Further RRA after endoscopic therapy was endoscopically treatable in most cases. Overall, only 9 (4.2%, 95% CI 2.2% to 7.8%) of 213 patients with RRA required surgery.Thus 159 (98.8%, 95% CI 95.1% to 99.8%) of 161 cases with initially successful endoscopic treatment of RRA and follow-up remained surgery-free for a median of 13 months (IQR 25.0) of follow-up. CONCLUSIONS: RRA after EMR of LNPCPs can be effectively treated using simple endoscopic techniques with long-term adenoma remission of >90%; only 16% required retreatment. Therefore, more technically complex, morbid and resource-intensive endoscopic or surgical techniques are required only in selected cases. TRIAL REGISTRATION NUMBERS: NCT01368289 and NCT02000141.

Endoscopic resection-related colorectal strictures: risk factors, management, and long-term outcomes.

INTRODUCTION: Colorectal strictures related to endoscopic resection (ER) of large nonpedunculated colorectal polyps (LNPCPs) may be problematic. Data on prevalence, risk factors, and management are limited. We report a prospective study of colorectal strictures following ER and describe our approach to management. METHODS: We analyzed prospectively collected data over 150 months, until June 2021, for patients who underwent ER for LNPCPs ≥ 40 mm. The ER defect size was graded as < 60 %, 60 %-89 %, or ≥ 90 % of the luminal circumference. Strictures were considered "severe" if patients experienced obstructive symptoms, "moderate" if an adult colonoscope could not pass the stenosis, or "mild" if there was resistance on successful passage. Primary outcomes included stricture prevalence, risk factors, and management. RESULTS: 916 LNPCPs ≥ 40 mm in 916 patients were included (median age 69 years, interquartile range 61-76 years, male sex 484 [52.8 %]). The primary resection modality was endoscopic mucosal resection in 859 (93.8 %). Risk of stricture formation with an ER defect ≥ 90 %, 60 %-89 %, and < 60 % was 74.2 % (23/31), 25.0 % (22/88), and 0.8 % (6 /797), respectively. Severe strictures only occurred with ER defects ≥ 90 % (22.6 %, 7/31). Defects < 60 % conferred low risk of only mild strictures (0.8 %, 6/797). Severe strictures required earlier (median 0.9 vs. 4.9 months; P = 0.01) and more frequent (median 3 vs. 2; P = 0.02) balloon dilations than moderate strictures. CONCLUSION: Most patients with ER defects ≥ 90 % of luminal circumference developed strictures, many of which were severe and required early balloon dilation. There was minimal risk with ER defects < 60 %.

A Rectum-Specific Selective Resection Algorithm Optimizes Oncologic Outcomes for Large Nonpedunculated Rectal Polyps.

BACKGROUND AND AIMS: Endoscopic mucosal resection (EMR) and endoscopic submucosal dissection (ESD) are complementary techniques for large (≥20 mm) nonpedunculated rectal polyps (LNPRPs). A mechanism for appropriate technique selection has not been described. METHODS: We evaluated the performance of a selective resection algorithm (SRA) (August 2017 to April 2021) compared with a universal EMR algorithm (UEA) (July 2008 to July 2017) for LNPRPs within a prospective observational study. In the SRA, LNPRPs with features of superficial submucosal invasive cancer (SMIC) (<1000 µm; Kudo pit pattern Vi), or with an increased risk of SMIC (Paris 0-Is or 0-IIa+Is nongranular, 0-IIa+Is granular with a dominant nodule ≥10 mm) underwent ESD. The remaining LNPRPs underwent EMR. Algorithm performance was evaluated by SMIC identified after EMR, curative oncologic resection (R0 resection, superficial SMIC, absence of negative histologic features), technical success, adverse events, and recurrence at first surveillance colonoscopy. RESULTS: A total of 480 LNPRPs were evaluated (290 UEA, 190 SRA). Median lesion size was 40 (interquartile range, 30-60) mm. SMIC was identified in 56 (11.7%) LNPRPs. Significant differences in SMIC after EMR (SRA 1 [1.0%] vs UEA 35 [12.1%]; P = .001) and curative oncologic resection (SRA n = 7 [33.3%] vs UEA n = 2 [5.7%]; P = .010) were identified. No significant differences in technical success or adverse events were identified (all P > .137). Among LNPRPs with SMIC amenable to curative oncologic resection and which underwent ESD, 100% (n = 7 of 7) were cured. CONCLUSIONS: A rectum-specific SRA optimizes oncologic outcomes for LNPRPs and mitigates the risk of piecemeal resection of cancers.

Vessel and tissue recognition during third-space endoscopy using a deep learning algorithm.

In this study, we aimed to develop an artificial intelligence clinical decision support solution to mitigate operator-dependent limitations during complex endoscopic procedures such as endoscopic submucosal dissection and peroral endoscopic myotomy, for example, bleeding and perforation. A DeepLabv3-based model was trained to delineate vessels, tissue structures and instruments on endoscopic still images from such procedures. The mean cross-validated Intersection over Union and Dice Score were 63% and 76%, respectively. Applied to standardised video clips from third-space endoscopic procedures, the algorithm showed a mean vessel detection rate of 85% with a false-positive rate of 0.75/min. These performance statistics suggest a potential clinical benefit for procedure safety, time and also training.

Comparison of the morphology and histopathology of large nonpedunculated colorectal polyps in the rectum and colon: implications for endoscopic treatment.

BACKGROUND AND AIMS: The risk of cancer in large nonpedunculated colorectal polyps ≥20 mm (LNPCPs) in the rectum relative to the remainder of the colon is unknown. We aimed to describe differences between rectal and colonic LNPCPs to better inform treatment decisions. METHODS: Patients with LNPCPs referred to tertiary centers for endoscopic resection within a prospective, multicenter, observational cohort were evaluated. Data recorded were participant demographics, LNPCP location, morphology, resection modality, and histopathologic data. Multiple logistic regression analysis was used to identify those variables independently associated with rectal versus nonrectal location in the colon. RESULTS: Patients with LNPCPs referred for endoscopic resection between July 2008 and July 2021 were included. Rectal LNPCPs (n = 618) were larger (median size, 40 mm vs 30 mm; P < .001) and more likely to be granular (79% vs 50%, P < .001) with a nodular component (53% vs 17%, P < .001) compared with nonrectal LNPCPs (n = 2787). Rectal LNPCPs were more likely to have tubulovillous histopathology (72% vs 47%, P < .001) and contain cancer (15% vs 6%, P < .001). After adjusting for the other features independently associated with location, cancer was more common in the rectum compared with the colon (odds ratio, 1.77; 95% confidence interval, 1.25-2.53). CONCLUSIONS: This study suggests that compared with LNPCPs in the rest of the colon, rectal LNPCPs are more likely to be larger and contain more advanced pathology. These findings have implications for curative endoscopic resection techniques particularly where early cancer is present. (Clinical trial registration numbers: NCT01368289 and NCT02000141.).

Clinical outcome of non-curative endoscopic submucosal dissection for early colorectal cancer.

OBJECTIVE: Endoscopic submucosal dissection (ESD) in a curative intent for submucosa-invasive early (T1) colorectal cancers (T1-CRCs) often leads to subsequent surgical resection in case of histologic parameters indicating higher risk of nodal involvement. In some cases, however, the expected benefit may be offset by the surgical risks, suggesting a more conservative approach. DESIGN: Retrospective analysis of consecutive patients with T1-CRC who underwent ESD at 13 centres ending inclusion in 2019 (n=3373). Cases with high risk of nodal involvement (non-curative ESD: G3, submucosal invasion>1000 µm, lymphovascular involvement, budding or incomplete resection/R1) were analysed if follow-up data (endoscopy/imaging) were available, regardless of the postendoscopic management (follow-up vs surgery) selected by the multidisciplinary teams in these institutions. Comorbidities were classified according to Charlson Comorbidity Index (CCI). Outcomes were disease recurrence, death and disease-related death rates in the two groups. Rate of residual disease (RD) at both the previous resection site and regional lymph nodes was assessed in the surgical cases as well as from follow-up in the follow-up group. RESULTS: Of 604 patients treated by colorectal ESD for submucosally invasive cancer, 207 non-curative resections (34.3%) were included (138 male; mean age 67.6±10.9 years); in 65.2% of cases, no complete resection was achieved (R1). Of the 207 cases, 60.9% (n=126; median CCI: 3; IQR: 2-4) underwent surgical treatment with RD in 19.8% (25/126), while 39.1% (n=81, median CCI: 5; IQR: 4-6) were followed up by endoscopy in all cases. Patients in the follow-up group had a higher overall mortality (HR=3.95) due to non-CRC causes (n=9, mean survival after ESD 23.7±13.7 months). During this follow-up time, tumour recurrence and disease-specific survival rates were not different between the groups (median follow-up 30 months; range: 6-105). CONCLUSION: Following ESD for a lesion at high risk of RD, follow-up only may be a reasonable choice in patients at high risk for surgery. Also, endoscopic resection quality should be improved. TRIAL REGISTRATION NUMBER: NCT03987828.

Outcomes of Deep Mural Injury After Endoscopic Resection: An International Cohort of 3717 Large Non-Pedunculated Colorectal Polyps.

BACKGROUND & AIMS: Although perforation is the most feared adverse event associated with endoscopic mucosal resection (EMR), limited data exists concerning its management. Therefore, we sought to evaluate the short- and long-term outcomes of intra-procedural deep mural injury (DMI) in an international multi-center observational cohort of large (≥20 mm) non-pedunculated colorectal polyps (LNPCPs). METHODS: Consecutive patients who underwent EMR for a LNPCP ≥20 mm were evaluated. Significant DMI (S-DMI) was defined as Sydney DMI Classification type III (muscularis propria injury, target sign) or type IV/V (perforation without or with contamination, respectively). The primary outcome was successful S-DMI defect closure. Secondary outcomes included technical success (removal of all visible polypoid tissue during index EMR), surgical referral and recurrence at first surveillance colonscopy (SC1). RESULTS: Between July 2008 to May 2020, 3717 LNPCPs underwent EMR. Median lesion size was 35mm (interquartile range (IQR) 25 to 45mm). Significant DMI was identified in 101 cases (2.7%), with successful defect closure in 98 (97.0%) using a median of 4 through-the-scope clips (TTSCs; IQR 3 to 6 TTSCs). Three (3.0%) patients underwent S-DMI-related urgent surgery. Technical success was achieved in 94 (93.1%) patients, with 46 (45.5%) admitted to hospital (median duration 1 day; IQR 1 to 2 days). Comparing LNPCPs with and without S-DMI, no differences in technical success (94 (93.1%) vs 3316 (91.7%); P = .62) or SC1 recurrence (12 (20.0%) vs 363 (13.6%); P = .15) were identified. CONCLUSIONS: Significant DMI is readily managed endoscopically and does not appear to affect technical success or recurrence.

Simple optical evaluation criteria reliably identify the post-endoscopic mucosal resection scar for benign large non-pedunculated colorectal polyps without tattoo placement.

BACKGROUND: Recognition of the post-endoscopic mucosal resection (EMR) scar is critical for large (≥ 20 mm) non-pedunculated colorectal polyp (LNPCP) management. The utility of intraluminal tattooing to facilitate scar identification is unknown. METHODS: We evaluated the ability of simple easy-to-use optical evaluation criteria to detect the post-EMR scar, with or without tattoo placement, in a prospective observational cohort of LNPCPs referred for endoscopic resection. The primary outcome was scar identification, further stratified by lesion size (20-39 mm, ≥ 40 mm) and histopathology (adenomatous, serrated). RESULTS: 1023 LNPCPs underwent both successful EMR and first surveillance colonoscopy (median size 35 mm, IQR 30-50 mm); 124 (12.1 %) had an existing tattoo or a tattoo placed at the index EMR. The post-EMR scar was identified in 1020 patients (99.7 %). The presence of a tattoo did not affect scar identification (100.0 % vs. 99.7 %; P > 0.99). There was no difference for LNPCPs 20-39 mm, LNPCPs ≥ 40 mm, adenomatous LNPCPs, and serrated LNPCPs (all P > 0.99). CONCLUSIONS: The post-EMR scar can be reliably identified with simple easy-to-use optical evaluation criteria, without the need for universal tattoo placement.