Cold versus hot snare endoscopic mucosal resection for large (≥15 mm) flat non-pedunculated colorectal polyps: a randomised controlled trial.

BACKGROUND AND AIMS: Conventional hot snare endoscopic mucosal resection (H-EMR) is effective for the management of large (≥20 mm) non-pedunculated colon polyps (LNPCPs) however, electrocautery-related complications may incur significant morbidity. With a superior safety profile, cold snare EMR (C-EMR) of LNPCPs is an attractive alternative however evidence is lacking. We conducted a randomised trial to compare the efficacy and safety of C-EMR to H-EMR. METHODS: Flat, 15-50 mm adenomatous LNPCPs were prospectively enrolled and randomly assigned to C-EMR or H-EMR with margin thermal ablation at a single tertiary centre. The primary outcome was endoscopically visible and/or histologically confirmed recurrence at 6 months surveillance colonoscopy. Secondary outcomes were clinically significant post-EMR bleeding (CSPEB), delayed perforation and technical success. RESULTS: 177 LNPCPs in 177 patients were randomised to C-EMR arm (n=87) or H-EMR (n=90). Treatment groups were equivalent for technical success 86/87 (98.9%) C-EMR versus H-EMR 90/90 (100%); p=0.31. Recurrence was significantly greater in C-EMR (16/87, 18.4% vs 1/90, 1.1%; relative risk (RR) 16.6, 95% CI 2.24 to 122; p<0.001).Delayed perforation (1/90 (1.1%) vs 0; p=0.32) only occurred in the H-EMR group. CSPEB was significantly greater in the H-EMR arm (7/90 (7.8%) vs 1/87 (1.1%); RR 6.77, 95% CI 0.85 to 53.9; p=0.034). CONCLUSION: Compared with 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. TRIAL REGISTRATION NUMBER: NCT04138030.

Endoscopic resection of large anastomotic polyps is safe and effective.

BACKGROUND: Large (≥20mm) adenomatous anastomotic polyps (LAAPs) are uncommon. Data pertaining to their prevalence, characteristics, and the efficacy of endoscopic resection (ER) are absent. A safe and effective strategy for ER would reduce morbidity and healthcare costs. METHODS: Large nonpedunculated colorectal polyps of ≥20mm (LNPCPs) referred for ER were prospectively studied. Multiple data points were recorded including anastomotic location, polyp morphology, resection modality, complications, and technical success. RESULTS: Over 7 years until November 2022, 2629 lesions were referred. Of these, 10 (0.4%) were LAAPs (median size 35 mm [interquartile range (IQR) 30-40mm]). All LAAPs were removed by piecemeal endoscopic mucosal resection (EMR), most (n=9; 90%) in combination with cold-forceps avulsion with adjuvant snare-tip soft coagulation (CAST). On comparison of the LAAP group with the conventional LNPCP group, CAST was more commonly used (90% vs. 9%; P<0.001) and deep mural injury (DMI) type II was more frequent (40% vs. 11%, P=0.003); however, significant DMI (III-V) did not occur. At 6 month (IQR 5.25-6 months) surveillance, there was no recurrence in any of the 10 cases. There were no serious adverse events. CONCLUSIONS: LAAPs present unique challenges owing to their location overlying an anastomosis. Despite these challenges they can be safely and effectively managed endoscopically without recurrence at endoscopic follow-up.

Geometry of cold snare polypectomy and risk of incomplete resection.

BACKGROUND: Cold snare polypectomy (CSP) is safer than and equally efficacious as hot snare polypectomy (HSP) for the removal of small (<10mm) colorectal polyps. The maximum polyp size that can be effectively managed by piecemeal CSP (p-CSP) without an excessive burden of recurrence is unknown. METHODS: Resection error risks (RERs), defined as the estimated likelihood of incomplete removal of adenomatous tissue for a single snare resection pass, for CSP and HSP were calculated, based on an incomplete resection rate. Polyp area, snare size, estimated number of resections, and optimal resection defect area were modeled. Overall risk of incomplete resection (RIR) was defined as RIR=1 - (1 - p)n, where p is the RER and n the number of resections. RESULTS: A 40-mm polyp has a four times greater area than a 20-mm polyp (314.16mm2 vs. 1256.64mm2), and requires three times more resections (11 vs. 33, respectively, assuming 8-mm piecemeal resection pieces for p-CSP). RIRs for a 40-mm polyp by HSP and p-CSP were 15.1%-23% and 40.74%-60.60% respectively. CONCLUSION: RER is more important with p-CSP than with HSP. The number of resections, n, and consequently RIR increases with increasing polyp size. Given the overwhelming safety of CSP, specific techniques to minimize the RER should be studied and developed.

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.

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.

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 %.

Novel Isoform DTX3c Associates with UBE2N-UBA1 and Cdc48/p97 as Part of the EphB4 Degradation Complex Regulated by the Autocrine IGF-II/IRA Signal in Malignant Mesothelioma.

EphB4 angiogenic kinase over-expression in Mesothelioma cells relies upon a degradation rescue signal provided by autocrine IGF-II activation of Insulin Receptor A. However, the identity of the molecular machinery involved in EphB4 rapid degradation upon IGF-II signal deprivation are unknown. Using targeted proteomics, protein-protein interaction methods, PCR cloning, and 3D modeling approaches, we identified a novel ubiquitin E3 ligase complex recruited by the EphB4 C tail upon autocrine IGF-II signal deprivation. We show this complex to contain a previously unknown N-Terminal isoform of Deltex3 E3-Ub ligase (referred as "DTX3c"), along with UBA1(E1) and UBE2N(E2) ubiquitin ligases and the ATPase/unfoldase Cdc48/p97. Upon autocrine IGF-II neutralization in cultured MSTO211H (a Malignant Mesothelioma cell line that is highly responsive to the EphB4 degradation rescue IGF-II signal), the inter-molecular interactions between these factors were enhanced and their association with the EphB4 C-tail increased consistently with the previously described EphB4 degradation pattern. The ATPase/unfoldase activity of Cdc48/p97 was required for EphB4 recruitment. As compared to the previously known isoforms DTX3a and DTX3b, a 3D modeling analysis of the DTX3c Nt domain showed a unique 3D folding supporting isoform-specific biological function(s). We shed light on the molecular machinery associated with autocrine IGF-II regulation of oncogenic EphB4 kinase expression in a previously characterized IGF-II+/EphB4+ Mesothelioma cell line. The study provides early evidence for DTX3 Ub-E3 ligase involvement beyond the Notch signaling pathway.

Outcomes of Thermal Ablation of the Mucosal Defect Margin After Endoscopic Mucosal Resection: A Prospective, International, Multicenter Trial of 1000 Large Nonpedunculated Colorectal Polyps.

BACKGROUND & AIMS: Thermal ablation of the defect margin after endoscopic mucosal resection (EMR-T) for treating large (≥20 mm) nonpedunculated colorectal polyps (LNPCPs) has shown efficacy in a randomized trial, with a 4-fold reduction, in residual or recurrent adenoma (RRA) at first surveillance colonoscopy (SC1). The clinical effectiveness of this treatment, in the real world, remains unknown. METHODS: We sought to evaluate the effectiveness of EMR-T in an international multicenter prospective trial (NCT02957058). The primary endpoint was the frequency of RRA at SC1. Detailed demographic, procedural, and outcome data were recorded. Exclusion criteria were LNPCPs involving the ileo-caecal valve, the appendiceal orifice, and circumferential LNPCPs. RESULTS: During 51 months (May 2016-August 2020) 1049 LNPCPs in 1049 patients (median size, 35 mm; interquartile range, 25-45 mm; right colon location, 53.5%) were enrolled. Uniform completeness of EMR-T was achieved in 989 LNPCPs (95.4%). In this study, 755/803 (94.0%) eligible LNPCPs underwent SC1 (median time to SC1, 6 months; interquartile range, 5-7 months). For LNPCPs that underwent complete EMR-T, the frequency of RRA at SC1 was 1.4% (10/707). CONCLUSIONS: In clinical practice, EMR-T is a simple, inexpensive, and highly effective auxiliary technique that is likely to significantly reduce RRA at first surveillance. It should be universally used for the management of LNPCPs after EMR. https://clinicaltrials.gov; Clinical Trial Number, NCT02957058.

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.

Transcriptional and Post-Translational Control Mechanisms for EphB4 Expression in Physiology and Cancer Disease.

EphB4 is a membrane tyrosine kinase receptor involved in a number of physiologic and pathologic conditions, cancer being the one drawing the highest attention. In mammalians, EphB4 regulates blood vessel growth and differentiation. EphB4 also mediates a number of cancer promoting effects including angiogenesis, invasion, and metastasis. Its effects have been linked to both EphrinB2-dependent and to EphrinB2-independent mechanisms. In spite of its emerging role in physiology and disease, the regulation of EphB4 cellular expression has been poorly described until recently. The present mini-review summarizes the latest findings on EphB4 regulation at the transcriptional and post-transcriptional level and discusses the biologic implications of such novel findings. Perspective on the scenarios opened by such findings and the open questions in EphB4 research is also provided.

Previously Attempted Large Nonpedunculated Colorectal Polyps Are Effectively Managed by Endoscopic Mucosal Resection.

INTRODUCTION: Endoscopic mucosal resection (EMR) is an effective therapy for naive large nonpedunculated colorectal polyps (N-LNPCPs). The best approach for the treatment of previously attempted LNPCPs (PA-LNPCPs) is undetermined. METHODS: EMR performance for PA-LNPCPs was evaluated in a prospective observational cohort of LNPCPs ≥20 mm. Efficacy was measured by technical success (removal of all visible polypoid tissue during index EMR) and recurrence at first surveillance colonoscopy (SC1). Safety was assessed by clinically significant intraprocedural bleeding, deep mural injury types III-V, clinically significant post-EMR bleeding, and delayed perforation. RESULTS: From January 2012 to October 2019, 158 PA-LNPCPs and 1,134 N-LNPCPs underwent EMR. Median PA-LNPCP size was 30 mm (interquartile range 25-46 mm). Technical success was 93.0% and increased to 95.6% after adjusting for 2-stage EMR. Cold-forceps avulsion with adjuvant snare-tip soft coagulation (CAST) was required for nonlifting polypoid tissue in 73 (46.2%). Median time to SC1 was 6 months (interquartile range 5-7 months). Recurrence occurred in 9 (7.8%). No recurrence was identified among 65 PA-LNPCPs which underwent margin thermal ablation at SC1 vs 9 (18.0%; P < 0.001) which did not. There were significant differences in resection duration (35 vs 25 minutes; P < 0.001), technical success (93.0% vs 96.6%; P = 0.026), and use of CAST (46.2% vs 7.6%; P < 0.001), between PA-LNPCPs and N-LNPCPs. When adjusting for 2-stage EMR, no difference in technical success was identified (95.6% vs 97.8%; P = 0.100). No differences in adverse events or recurrence were identified. DISCUSSION: EMR, using auxillary techniques where necessary, can achieve high technical success and low recurrence frequencies for PA-LNPCPs.

Impact of technical innovations in EMR in the treatment of large nonpedunculated polyps involving the ileocecal valve (with video).

BACKGROUND AND AIMS: The endoscopic management of large nonpedunculated colorectal polyps involving the ileocecal valve (ICV-LNPCPs) remains challenging because of its unique anatomic features, with long-term outcomes inferior to LNPCPs not involving the ICV. We sought to evaluate the impact of technical innovations and advances in the EMR of ICV-LNPCPs. METHODS: The performance of EMR for ICV-LNPCPs was retrospectively evaluated in a prospective observational cohort of LNPCPs ≥20 mm. Efficacy was measured by clinical success (removal of all polypoid tissue during index EMR and avoidance of surgery) and recurrence at first surveillance colonoscopy. Accounting for the adoption of technical innovations, comparisons were made between an historical cohort (September 2008 to April 2016) and contemporary cohort (May 2016 to October 2020). Safety was evaluated by documenting the frequencies of intraprocedural bleeding, delayed bleeding, deep mural injury, and delayed perforation. RESULTS: Between September 2008 to October 2020, 142 ICV-LNPCPs were referred for EMR. Median ICV-LNPCP size was 35 mm (interquartile range, 25-50 mm). When comparing the contemporary (n = 66) and historical cohorts (n = 76) of ICV-LNPCPs, there were significant differences in clinical success (93.9% vs 77.6%, P = .006) and recurrence (4.6% vs 21.0%, P = .019). CONCLUSIONS: With technical advances, ICV-LNPCPs can be effectively and safely managed by EMR, independent of lesion complexity. Most patients experience excellent outcomes and avoid surgery.

Thermal Ablation of Mucosal Defect Margins Reduces Adenoma Recurrence After Colonic Endoscopic Mucosal Resection.

BACKGROUND & AIMS: Colorectal cancer (CRC) can be prevented by colonoscopy and polypectomy. Endoscopic mucosal resection (EMR) is performed to remove large laterally spreading colonic lesions that have a high risk of progression to CRC. Endoscopically invisible micro-adenomas at the margins of the EMR site might contribute to adenoma recurrence, which occurs in 15% to 30% of patients who undergo surveillance. We aimed to determine the efficacy of adjuvant thermal ablation of the EMR mucosal defect margin in reducing polyp recurrence. METHODS: We performed a prospective study of 390 patients with large laterally spreading colonic lesions (≥ 20 mm, n = 416) referred for EMR at 4 tertiary centers in Australia. After complete lesion excision by EMR, lesions were randomly assigned to thermal ablation of the post-EMR mucosal defect margin (n = 210) or no additional treatment (controls, n = 206). We performed surveillance colonoscopies with standardized photo documentation and biopsies of the scar after 5 to 6 months. Patient, procedure, and lesion characteristics were similar between the groups. The primary endpoint was detection of lesion recurrence at first surveillance colonoscopy. RESULTS: A significantly lower proportion of patients who received thermal ablation of the post-EMR mucosal defect margin had evidence of recurrence at first surveillance colonoscopy (10/192, 5.2%) than controls (37/176, 21.0%) (P < .001). The relative risk of recurrence in the thermal ablation group was 0.25 compared with the control group (95% confidence interval 0.13-0.48). Rates of adverse events were similar between the groups. CONCLUSIONS: In a multicenter randomized trial, thermal ablation of the post-EMR mucosal defect margin significantly reduced polyp recurrence at first surveillance colonoscopy, compared with no additional treatment. Routine implementation of this simple and safe technique could increase the utility of EMR, decrease surveillance burdens, and reduce morbidity and mortality from CRC. ClinicalTrials.gov no: NCT01789749.

Impact of en bloc resection on long-term outcomes after endoscopic mucosal resection: a matched cohort study.

BACKGROUND AND AIMS: Residual or recurrent adenoma (RRA) is the major limitation of piecemeal EMR (p-EMR) for large colonic laterally spreading lesions (LSLs) ≥20 mm. En bloc EMR (e-EMR) has been shown to achieve low rates of RRA but specific procedural and long-term outcomes are unknown. Our aim was to compare long-term outcomes of size-matched LSLs stratified by whether they were resected e-EMR or p-EMR. METHODS: Data from a prospective tertiary referral multicenter cohort of large LSLs referred for EMR over a 10-year period were analyzed. Outcomes were compared between sized-matched LSLs (20-25 mm) resected by p-EMR or e-EMR. RESULTS: Five hundred seventy LSLs met the inclusion criteria of which 259 (45.4%) were resected by e-EMR. The risk of major deep mural injury (DMI) was significantly higher in the e-EMR group (3.5% vs 1.0%, P = .05), whereas rates of other intraprocedural adverse events did not differ significantly. Five of 9 (56%) LSLs, with endoscopic features of submucosal invasion (SMI), resected by e-EMR were saved from surgery. RRA at first surveillance was lower in the e-EMR group (2.0% vs 5.7%, P = .04), but this difference was negated at subsequent surveillance. Rates of surgical referral were not significantly different between the groups at either surveillance interval. CONCLUSION: When comparing e-EMR against p-EMR for lesions ≤25 mm in size of similar morphology in a large prospective multicenter cohort, e-EMR offered no additional advantage for predicted-benign LSLs. However, it was associated with an increased risk of major DMI. Thus, en bloc resection techniques should be reserved for lesions suspicious for invasive disease. (Clinical trial registration number: NCT01368289.).

Wide-field endoscopic mucosal resection versus endoscopic submucosal dissection for laterally spreading colorectal lesions: a cost-effectiveness analysis.

OBJECTIVE: To compare the cost-effectiveness of endoscopic submucosal dissection (ESD) and wide-field endoscopic mucosal resection (WF-EMR) for removing large sessile and laterally spreading colorectal lesions (LSLs) >20 mm. DESIGN: An incremental cost-effectiveness analysis using a decision tree model was performed over an 18-month time horizon. The following strategies were compared: WF-EMR, universal ESD (U-ESD) and selective ESD (S-ESD) for lesions highly suspicious for containing submucosal invasive cancer (SMIC), with WF-EMR used for the remainder. Data from a large Western cohort and the literature were used to inform the model. Effectiveness was defined as the number of surgeries avoided per 1000 cases. Incremental costs per surgery avoided are presented. Sensitivity and scenario analyses were performed. RESULTS: 1723 lesions among 1765 patients were analysed. The prevalence of SMIC and low-risk-SMIC was 8.2% and 3.1%, respectively. Endoscopic lesion assessment for SMIC had a sensitivity and specificity of 34.9% and 98.4%, respectively. S-ESD was the least expensive strategy and was also more effective than WF-EMR by preventing 19 additional surgeries per 1000 cases. 43 ESD procedures would be required in an S-ESD strategy. U-ESD would prevent another 13 surgeries compared with S-ESD, at an incremental cost per surgery avoided of US$210 112. U-ESD was only cost-effective among higher risk rectal lesions. CONCLUSION: S-ESD is the preferred treatment strategy. However, only 43 ESDs are required per 1000 LSLs. U-ESD cannot be justified beyond high-risk rectal lesions. WF-EMR remains an effective and safe treatment option for most LSLs. TRIAL REGISTRATION NUMBER: NCT02000141.

Risk Stratification for Covert Invasive Cancer Among Patients Referred for Colonic Endoscopic Mucosal Resection: A Large Multicenter Cohort.

BACKGROUND & AIMS: Among patients with large colorectal sessile polyps or laterally spreading lesions, it is important to identify those at risk for submucosal invasive cancer (SMIC). Lesions with overt endoscopic evidence of SMIC are referred for surgery, although those without these features might still contain SMIC that is not visible on endoscopic inspection (covert SMIC). Lesions with a high covert SMIC risk might be better suited for endoscopic submucosal dissection than for endoscopic mucosal resection (EMR). We analyzed a group of patients with large colon lesions to identify factors associated with SMIC, and examined lesions without overt endoscopic high-risk signs to determine factors associated with covert SMIC. METHODS: We performed a prospective cohort study of consecutive patients referred for EMR of large sessile or flat colorectal polyps or laterally spreading lesions (≥20 mm) at academic hospitals in Australia from September 2008 through September 2016. We collected data on patient and lesion characteristics, outcomes of procedures, and histology findings. We excluded serrated lesions from the analysis of covert SMIC due to their distinct phenotype and biologic features. RESULTS: We analyzed 2277 lesions (mean size, 36.9 mm) from 2106 patients (mean age, 67.7 years; 53.2% male). SMIC was evident in 171 lesions (7.6%). Factors associated with SMIC included Kudo pit pattern V, a depressed component (0-IIc), rectosigmoid location, 0-Is or 0-IIa+Is Paris classification, non-granular surface morphology, and increasing size. After exclusion of lesions that were obviously SMIC or serrated, factors associated with covert SMIC were rectosigmoid location (odds ratio, 1.87; P = .01), combined Paris classification, surface morphology (odds ratios, 3.96-22.5), and increasing size (odds ratio, 1.16/10 mm; P = .012). CONCLUSIONS: In a prospective study of 2106 patients who underwent EMR for large sessile or flat colorectal polyps or laterally spreading lesions, we associated rectosigmoid location, combined Paris classification and surface morphology, and increasing size with increased risk for covert malignancy. Rectosigmoid 0-Is and 0-IIa+Is non-granular lesions have a high risk for malignancy, whereas proximally located 0-Is or 0-IIa granular lesions have a low risk. These findings can be used to inform decisions on which patients should undergo endoscopic submucosal dissection, EMR, or surgery. ClinicalTrials.gov, Number: NCT02000141.

EMR of laterally spreading lesions around or involving the appendiceal orifice: technique, risk factors for failure, and outcomes of a tertiary referral cohort (with video).

BACKGROUND AND AIMS: EMR of sessile periappendiceal laterally spreading lesions (PA-LSLs) is technically demanding because of poor endoscopic access to the appendiceal lumen and the thin colonic wall at the base of the cecum. We aimed to assess the feasibility and safety of EMR for PA-LSLs. METHODS: Consecutive LSLs ≥20 mm and PA-LSLs ≥10 mm detected at 3 academic endoscopy centers from September 2008 until January 2017 were eligible. Prospective patient, procedural, and lesion data were collected. PA-LSLs were compared with LSLs in other colonic locations. RESULTS: Thirty-eight PA-LSLs were compared with 1721 LSLs. Referral for surgery without an attempt at EMR was more likely with PA-LSLs (28.9% vs 5.1%, P < .001), and those that involved a greater percentage of the appendiceal orifice (AO) were less likely to be attempted (P = .038). Most PA-LSLs (10/11) were not attempted because of deep extension into the appendiceal lumen; 2 of 11 of these surgical specimens contained invasive cancer. Once attempted, complete clearance of visible adenoma (92.6% PA-LSLs vs 97.6% LSLs, P = .14), adverse events, and rates of adenoma recurrence did not vary significantly between PA-LSLs and LSLs. All 7 patients with prior appendicectomy achieved complete adenoma clearance. There were no cases of post-EMR appendicitis. Twenty of 22 PA-LSLs (91%) eligible for surveillance avoided surgery to longest follow-up. CONCLUSIONS: EMR is a safe, effective, and durable treatment for PA-LSLs when specific criteria are fulfilled. If the distal margin of the PA-LSL within the AO cannot be visualized or if more than 50% of the circumference of the orifice is involved, surgery should be considered. (Clinical trial registration number: NTC01368289.).

The clinical significance and synchronous polyp burden of large (≥ 20 mm) sessile serrated polyps in patients without serrated polyposis syndrome.

BACKGROUND: Sessile serrated polyps (SSPs) are important precursors of colorectal carcinoma and interval cancer. Large SSPs (≥ 20 mm) outside the definition of serrated polyposis syndrome (SPS) have not been studied in comparison with SPS. We aimed to describe the characteristics of patients with large SSPs in this context. METHODS: Patients with at least one SSP (≥ 20 mm) were eligible. Data from three consecutive colonoscopies were used to compare clinical and endoscopic characteristics in three patient groups: SPS, a solitary large SSP, and patients with at least two SSPs without fulfilling the criteria for SPS (oligo-SSP). Data on the diagnostic colonoscopy were collected retrospectively, whereas the remaining data was collected prospectively. RESULTS: 67/146 patients (45.9 %) had SPS, 53/146 (36.3 %) had a solitary SSP, and 26/146 (17.8 %) were categorized as oligo-SSP. Personal (16.4 %, 9.4 %, and 11.5 %, respectively) and family (17.9 %, 17.0 %, and 23.1 %, respectively) history of colorectal carcinoma did not differ significantly between groups. Polyp burden was greater in SPS compared with solitary SSP but was not different from oligo-SSP (advanced adenomas: SPS 32.8 % vs. solitary SSP 9.4 % [P = 0.002] vs. oligo-SSP 34.6 % [P = 0.87]; ≥ 10 conventional adenomas: 11.9 % vs. 0 % [P = 0.01] vs. 3.8 % [P = 0.44], respectively). Dysplasia in large SSPs was frequent in all groups (41.1 % overall). SPS was recognized by referring endoscopists in only 9.0 % of cases. CONCLUSION: Patients with oligo-SSPs have similar synchronous polyp burden and clinical characteristics as patients with SPS and may require similar surveillance. Modification of the criteria for the diagnosis of SPS to include this group seems warranted. Patients with a solitary SSP have a lower risk of synchronous polyps, including advanced adenomas. Larger studies are warranted to determine whether these patients may return to standard surveillance following complete examination and clearance of the colon.