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.

Long-term outcomes after endoscopic submucosal dissection for relative indication early gastric cancer in nonsurgical candidates.

BACKGROUND AND AIMS: Endoscopic submucosal dissection (ESD) is effective in treating early gastric cancer (EGC). Its role in patients with comorbidities along with more advanced disease is unknown. We sought to evaluate this in a large Western cohort. METHODS: Consecutive patients who underwent ESD for EGC in a single tertiary Western endoscopy center over 10 years were prospectively analyzed. The primary outcomes were long-term overall survival (OS) and disease-free survival (DFS) up to 5 years. Secondary outcomes were efficacy and serious adverse events (SAEs). RESULTS: ESD for 157 cases of EGC in 149 patients was performed in an elderly and comorbid cohort with a mean age of 73.7 years and age-adjusted Charlson Comorbidity Index of 4.2. Over a median follow-up of 51.6 months, no significant differences were found in 5-year OS (88.9% vs 77.9%, P = .290) and DFS (83.2% vs 75.1%, P = .593) between absolute indication (AI) EGC and relative indication (RI) EGC. The AI EGC cohort achieved higher en-bloc (96.3% vs 87.5%, P = .069) and R0 resection rates (93.6% vs 62.5%, P < .001) when compared with RI EGC. No significant differences were found in SAEs (7.3% vs 12.5%, P = .363). No mortality or surgical resection ensued from adverse events from ESD. CONCLUSIONS: ESD safely confers DFS in poor surgical candidates with RI EGC in a large Western cohort. Patients who are elderly and/or with comorbidities or decline surgical resection may benefit from ESD and avoid the risks of surgery and its long-term sequelae. (Clinical trial registration number: NCT02306707.).

Hybrid resection versus conventional resection for laterally spreading lesions of the papilla.

BACKGROUND AND AIMS: Although conventional hot snare resection (CR) of laterally spreading lesions of the major papilla (LSL-Ps) is effective, it can be associated with delayed bleeding in upward of 25% of cases. Given the excellent safety profile of cold snare polypectomy in the colorectum, we investigated the efficacy and safety of a novel hybrid resection (HR) technique for LSL-P management, consisting of hot snare papillectomy plus cold snare resection of the laterally spreading component. METHODS: A prospective cohort of patients underwent HR in a tertiary referral center over 60 months until December 2022. This cohort was compared with a historical cohort of patients who underwent CR at the same institution over 120 months until August 2017. The primary outcomes were recurrence and bleeding. RESULTS: Twenty patients underwent HR (14 female; mean age 65.2 ± 12.2 years). Median lesion size was 30 mm (interquartile range, 25.0-47.5 mm). Recurrent or residual adenoma (RRA) was greater with HR (58.8% [n = 10] vs 29.8% [n = 14]; P = .034). The odds ratio for recurrence was 3.6 times (95% CI, 1.2-11.0) higher with HR (P = .027). RRA was multifocal in 4 (40%) and had a composite RRA volume >10 mm in 7 (70%). The median number of procedures required to treat RRA was higher with HR (4 vs 1, P = .002). There was no difference between CR and HR for intraprocedural bleeding (41.1% [n = 23] vs 25% [n = 5]; P = .587) or delayed bleeding (25.0% vs 10.0%, P = .211). There were no perforations. CONCLUSIONS: The novel HR technique for LSL-P management is associated with a high rate of RRA that is recalcitrant to treatment, without mitigating the risk of intraprocedural or delayed bleeding. Therefore, CR should remain the mainstay management option for treating patients with an LSL-P. (Clinical trial registration number: NCT02306603.).

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.

Direct diverticular peroral endoscopic myotomy for the treatment of thoracic esophageal diverticula: technique and outcomes.

BACKGROUND: Diverticular peroral endoscopic myotomy (POEM) is an alternative to surgery for the management of symptomatic thoracic esophageal diverticula. Conventionally, this requires proximal tunnel formation but a direct approach may simplify the technique. Herein, we report the outcomes of direct diverticular-POEM (DD-POEM). METHODS: We conducted a single-center prospective observational study evaluating DD-POEM. This involved a direct approach to the diverticulum. Success was defined as an Eckardt score of ≤ 3 without the need for reintervention. RESULTS: 10 patients underwent DD-POEM (median age 72 years; interquartile range [IQR] 14.3; male 60 % [n = 6]). Median diverticulum size was 40 mm (IQR 7.5) and median location was 35 cm from the incisors (IQR 8.3). Five patients (50 %) had an underlying dysmotility disorder. The median procedure duration was 60 minutes (IQR 28.8). There were no adverse events. The median hospital stay was 1 day (IQR 0.75). The pre-procedure median Eckardt score of 6 (IQR 4) significantly improved to 0 (IQR 0.75; P < 0.001) at a median follow-up of 14.5 months (IQR 13.8). Success was achieved in all patients. CONCLUSIONS: DD-POEM was a safe technique for the management of thoracic esophageal diverticula. Owing to its simplicity and excellent performance it should be further evaluated for the treatment of this disorder.

When less is more: lower esophageal sphincter-preserving peroral endoscopic myotomy is effective for non-achalasia esophageal motility disorders.

BACKGROUND: Non-achalasia esophageal motility disorders (NAEMDs), encompassing distal esophageal spasm (DES) and hypercontractile esophagus (HCE), are rare conditions. Peroral endoscopic myotomy (POEM) is a promising treatment option. In NAEMDs, unlike with achalasia, the lower esophageal sphincter (LES) functions normally, suggesting the potential of LES preservation during POEM. METHODS: This retrospective two-center observational study focused on patients undergoing LES-preserving POEM (LES-POEM) for NAEMD. Eckardt scores were assessed pre-POEM and at 6, 12, and 24 months post-POEM, with follow-up endoscopy at 6 months to evaluate for reflux esophagitis. Clinical success, defined as an Eckardt score ≤3, served as the primary outcome. RESULTS: 227 patients were recruited over 84 months until May 2021. Of these, 16 underwent LES-POEM for an NAEMD (9 with HCE and 7 with DES). The median pre-POEM Eckardt score was 6.0 (interquartile range [IQR] 5.0-7.0), which decreased to 1.0 (IQR 0.0-1.8; P<0.001) 6 months post-POEM. This was sustained at 24 months, with an Eckardt score of 1.0 (IQR 0.0-1.8; P<0.001). Two patients (12.5%) developed Los Angeles grade A or B esophagitis. CONCLUSIONS: LES-POEM for NAEMD demonstrates favorable clinical outcomes, with infrequent esophagitis and reintervention for LES dysfunction rarely required.

A Sub-epithelial Lesion Algorithm For Endoscopic (SAFE) Resection In The Upper Gastrointestinal Tract.

INTRODUCTION: Complete excision of upper gastrointestinal sub-epithelial lesions (U-SELs) eliminates diagnostic uncertainty, obviates the need for surveillance and may be necessary for definitive diagnosis and management. Current guidelines lack precision and cohesion, and surgery is associated with significant morbidity. Herein, we describe and report on the outcomes of our SEL algorithm for endoscopic (SAFE) resection. METHODS: U-SELs were enrolled prospectively over 115 months until March 2023. All underwent axial (CT) imaging and endoscopic-ultrasonography (EUS) to exclude a large exophytic component or invasion into local structures, and assess for muscularis propria involvement. RESULTS: 106 U-SELs were resected (mean age 60.6±13.4, 51.9% male; 41 oesophageal, 65 gastric). Oesophageal U-SELs underwent ESD (n=22) or STER if MP involvement was suspected (n=19). Gastric U-SELs underwent STER (n=6 at cardia), ESD (n=47) or exposing-EFTR (n=12). Technical success was 97.6% and 92.3% respectively. Five (7.7%) were completed laparoscopically due to deep and broad full-thickness involvement. Five (7.7%) required laparoscopic gastrotomy and surgical retrieval after successful resection and closure due to a large lesion size (mean 47 mm). There was no delayed bleeding, perforation or recurrence at 13 months. CONCLUSION: U-SELs may be effectively and safely treated by endoscopic resection. The SAFE approach provides a framework that facilitates structured decision-making. Oesophageal U-SELs suspected to involve the MP should undergo STER. Gastric SELs can be best managed by ESD with a view to proceed to exposing-EFTR. A laparoscopic UGI surgeon should be available in case surgical retrieval of the specimen or laparoscopic completion is required.

A simplified algorithm to evaluate the risk of submucosal invasive cancer in large (≥20 mm) nonpedunculated colonic polyps.

BACKGROUND: Recognition of submucosal invasive cancer (SMIC) in large (≥20 mm) nonpedunculated colonic polyps (LNPCPs) informs selection of the optimal resection strategy. LNPCP location, morphology, and size influence the risk of SMIC; however, currently no meaningful application of this information has simplified the process to make it accessible and broadly applicable. We developed a decision-making algorithm to simplify the identification of LNPCP subtypes with increased risk of potential SMIC. METHODS: Patients referred for LNPCP resection from September 2008 to November 2022 were enrolled. LNPCPs with SMIC were identified from endoscopic resection specimens, lesion biopsies, or surgical outcomes. Decision tree analysis of lesion characteristics identified in multivariable analysis was used to create a hierarchical classification of SMIC prevalence. RESULTS: 2451 LNPCPs were analyzed: 1289 (52.6%) were flat, 1043 (42.6%) nodular, and 118 (4.8%) depressed. SMIC was confirmed in 273 of the LNPCPs (11.1%). It was associated with depressed and nodular vs. flat morphology (odds ratios [ORs] 35.7 [95%CI 22.6-56.5] and 3.5 [95%CI 2.6-4.9], respectively; P<0.001); rectosigmoid vs. proximal location (OR 3.2 [95%CI 2.5-4.1]; P<0.001); nongranular vs. granular appearance (OR 2.4 [95%CI 1.9-3.1]; P<0.001); and size (OR 1.12 per 10-mm increase [95%CI 1.05-1.19]; P<0.001). Decision tree analysis targeting SMIC identified eight terminal nodes: SMIC prevalence was 62% in depressed LNPCPs, 19% in nodular rectosigmoid LNPCPs, and 20% in nodular proximal colon nongranular LNPCPs. CONCLUSIONS: This decision-making algorithm simplifies identification of LNPCPs with an increased risk of potential SMIC. When combined with surface optical evaluation, it facilitates accurate lesion characterization and resection choices.

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.

The Surface Morphology of Large Nonpedunculated Colonic Polyps Predicts Synchronous Large Lesions.

BACKGROUND & AIMS: Large (≥20 mm) nonpedunculated colorectal polyps (LNPCPs) may have synchronous LNPCPs in up to 18% of cases. The nature of this relationship has not been investigated. We aimed to examine the relationship between individual LNPCP characteristics and synchronous colonic LNPCPs. METHODS: Consecutive patients referred for resection of LNPCPs over 130 months until March 2022 were enrolled. Serrated lesions and mixed granularity LNPCPs were excluded from analysis. Patients with multiple LNPCPs resected were identified, and the largest was labelled as dominant. The primary outcome was the identification of individual lesion characteristics associated with the presence of synchronous LNPCPs. RESULTS: There were 3149 of 3381 patients (93.1%) who had a single LNPCP. In 232 (6.9%) a synchronous lesion was detected. Solitary lesions had a median size of 35 mm with a predominant Paris 0-IIa morphology (42.9%) and right colon location (59.5%). In patients with ≥2 LNPCPs, the dominant lesion had a median size of 40 mm, Paris 0-IIa (47.6%) morphology, and right colon location (65.9%). In this group, 35.8% of dominant LNPCPs were non-granular compared with 18.7% in the solitary LNPCP cohort. Non-granular (NG)-LNPCPs were more likely to demonstrate synchronous disease, with left colon NG-LNPCPs demonstrating greater risk (odds ratio, 4.78; 95% confidence interval, 2.95-7.73) than right colon NG-LNPCPs (odds ratio, 1.99; 95% confidence interval, 1.39-2.86). CONCLUSIONS: We found that 6.9% of LNPCPs have synchronous disease, with NG-LNPCPs demonstrating a greater than 4-fold increased risk. With post-colonoscopy interval cancers exceeding 5%, endoscopists must be cognizant of an individual's LNPCP phenotype when examining the colon at both index procedure and surveillance. CLINICALTRIALS: gov, NCT01368289; NCT02000141; NCT02198729.

Cold snare EMR for the removal of large duodenal adenomas.

BACKGROUND AND AIMS: Large (≥15 mm) duodenal adenomas (DAs) are premalignant and require removal. Existing endoscopic resection techniques are compromised by serious adverse events (SAEs), most notably postprocedural bleeding (PPB) and perforation. To ameliorate these problems, we sought to evaluate the novel technique of cold snare EMR (CS-EMR) against the emerging standard of conventional EMR with thermal ablation of the postresection margin (EMR-T) for the safe and effective removal of DAs. METHODS: Consecutive patients were enrolled in a single tertiary center for CS-EMR and prospectively analyzed against a previously reported cohort of EMR-T from the same center. The primary outcome was rate of SAEs. Secondary outcomes were residual or recurrent adenoma at first surveillance endoscopy (SE1) at 6 months and technical success per lesion. RESULTS: Between October 2019 and July 2022, a total of 50 DAs ≥15 mm were removed via CS-EMR (median size, 30 mm [interquartile range (IQR), 19-40 mm]; mean ± standard deviation [SD] patient age, 70 ± 9.2 years) compared with 54 DAs via EMR-T (median size, 30 mm [IQR, 19-40 mm]; mean patient age, 68 ± 12.2 years). CS-EMR had a significantly lower rate of intraprocedural bleeding (2.0% vs 37%, P < .001) and PPB (4.0% vs 16.7%, P = .036). Two cases (4.0%) of immediate perforation occurred in CS-EMR; these were recognized immediately and closed with clips without sequelae. Total SAEs (16.0% vs 16.7%, P = 1) and technical success (100% vs 100%, P = 1) were identical. Recurrence at SE1 was significantly higher with CS-EMR (24.4% vs 2.3%, P = .002). CONCLUSIONS: CS-EMR reduces intraprocedural bleeding and PPB. However, it may increase the risk of immediate perforation and is associated with a significantly higher rate of recurrence at SE1. Further technical refinements are required to optimize endoscopic resection techniques for DAs. (Clinical trial registration number: NCT02306603.).

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 novel tool for case selection in endoscopic mucosal resection training.

BACKGROUND: As endoscopic mucosal resection (EMR) of large (≥ 20 mm) adenomatous nonpedunculated colonic polyps (LNPCPs) becomes widely practiced outside expert centers, appropriate training is necessary to avoid failed resection and inappropriate surgical referral. No EMR-specific tool guides case selection for endoscopists learning EMR. This study aimed to develop an EMR case selection score (EMR-CSS) to identify potentially challenging lesions for "EMR-naïve" endoscopists developing competency. METHODS: Consecutive EMRs were recruited from a single center over 130 months. Lesion characteristics, intraprocedural data, and adverse events were recorded. Challenging lesions with intraprocedural bleeding (IPB), intraprocedural perforation (IPP), or unsuccessful resection were identified and predictive variables identified. Significant variables were used to form a numerical score and receiver operating characteristic curves were used to generate cutoff values. RESULTS: Of 1993 LNPCPs, 286 (14.4 %) were in challenging locations (anorectal junction, ileocecal valve, or appendiceal orifice), 368 (18.5 %) procedures were complicated by IPB and 77 (3.9 %) by IPP; 110 (5.5 %) procedures were unsuccessful. The composite end point of IPB, IPP, or unsuccessful EMR was present in 526 cases (26.4 %). Lesion size, challenging location, and sessile morphology were predictive of the composite outcome. A six-point score was generated with a cutoff value of 2 demonstrating 81 % sensitivity across the training and validation cohorts. CONCLUSIONS: The EMR-CSS is a novel case selection tool for conventional EMR training, which identifies a subset of adenomatous LNPCPs that can be successfully and safely attempted in early EMR training.

Legal Approaches to New Psychoactive Substances: First Empirical Findings.

BACKGROUND: Generic drug legislation, i.e., simultaneously banning groups of drugs, has been introduced worldwide to counteract the trade and use of emerging "new psychoactive substances" (NPSs) more effectively. SUMMARY: The potential and de facto positive and negative effects of generic drug legislation have been described using an analysis based on documented evaluations of the experiences in the UK and Germany, supplemented with data from other publicly available sources. In particular, the effects of generic drug legislation on availability, use, sales, and overall health harms of NPS, and switches from NPS to traditional (classical) drugs are addressed. The results show that the introduction of generic drug legislation in the UK and Germany has enabled stricter regulation of NPS but has also led to some major harms within the domain of public health. Depending on the population considered, the rate of NPS use remained stable, slightly declined, or increased following the banning of NPS. Once banned, NPSs were more often purchased on the black market, often together with other (more harmful) drugs. Moreover, NPS-related harms did not reduce following the ban, and in some cases even increased. Finally, when harmful NPS, like potent synthetic opioids and cannabinoids, become substantially used and endanger public health, legislators already have the legal means to ban the problem drug, thus overruling the need for a generic ban. KEY MESSAGES: Generic drug legislation may facilitate drug law enforcement, but it is not (very) effective in counteracting NPS use and it may increase NPS-related public health problems. It is concluded that, overall, the advantages of generic drug legislation are overshadowed by its serious disadvantages.

Histopathological effects of electrosurgical interventions in an in vivo porcine model of colonic endoscopic mucosal resection.

OBJECTIVE: Endoscopic mucosal resection (EMR) in the colon has been widely adopted, but there is limited data on the histopathological effects of the differing electrosurgical currents (ESCs) used. We used an in vivo porcine model to compare the tissue effects of ESCs for snare resection and adjuvant margin ablation techniques. DESIGN: Standardised EMR was performed by a single endoscopist in 12 pigs. Two intersecting 15 mm snare resections were performed. Resections were randomised 1:1 using either a microprocessor-controlled current (MCC) or low-power coagulating current (LPCC). The lateral margins of each defect were treated with either argon plasma coagulation (APC) or snare tip soft coagulation (STSC). Colons were surgically removed at 72 hours. Two specialist pathologists blinded to the intervention assessed the specimens. RESULTS: 88 defects were analysed (median 7 per pig, median defect size 29×17 mm). For snare ESC effects, 156 tissue sections were assessed. LPCC was comparable to MCC for deep involvement of the colon wall. For margin ablation, 172 tissue sections were assessed. APC was comparable to STSC for deep involvement of the colon wall. Islands of preserved mucosa at the coagulated margin were more likely with APC compared with STSC (16% vs 5%, p=0.010). CONCLUSION: For snare resection, MCC and LPCC did not produce significantly different tissue effects. The submucosal injectate may protect the underlying tissue, and technique may more strongly dictate the depth and extent of final injury. For margin ablation, APC was less uniform and complete compared with STSC.

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.

A Randomized Controlled Trial of Cold Snare Polypectomy Technique: Technique Matters More Than Snare Wire Diameter.

INTRODUCTION: Cold snare polypectomy (CSP) is safe and effective for the removal of small adenomas (≤10 mm); however, reported incomplete resection rates (IRRs) vary. The optimal CSP technique, where a wide margin of normal tissue is resected around the target lesion, and snare design have both been hypothesized to reduce the IRR after CSP. We sought to investigate the efficacy of a thin-wire versus thick-wire diameter snare on IRR, using the standardized CSP technique. METHODS: This was an international multicenter parallel design randomized trial with 17 endoscopists of varying experience (NCT02581254). Patients were randomized in a 1:1 ratio to the use of a thin-wire (0.30 mm) or thick-wire (0.47 mm) snare for CSP of small (≤10 mm) colorectal polyps. The primary end point was the IRR as determined by the histologic assessment of the defect margin after polypectomy. RESULTS: Over 52 months to January 2020, 1,393 patients were eligible. A total of 660 patients with polyps (57.4% male) were randomized to a thin-wire (n = 339) or thick-wire (n = 321) snare. The overall IRR of the cohort was 1.5%. There was no significant difference in the IRR between the thin- and thick-wire arms; relative risk-0.41, 95% CI (0.11-1.56), P = 0.21. No significant differences were observed in the rate of adverse events. DISCUSSION: In this multicenter randomized trial, CSP is safe and effective with very low rates of incomplete resection independent of the diameter of the snare wire used. This suggests that the optimal operator technique is more important than the snare design alone in minimizing residual adenoma after CSP.