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

BACKGROUND AND AIMS: Endoscopic submucosal dissection (ESD) is effective in treating early gastric cancer (EGC). It's role in the comorbid 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 centre 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 (SAE). RESULTS: ESD for 157 EGC in 149 patients were performed in an elderly and comorbid cohort with mean age 73.7 years and age-adjusted Charleson Comorbidity Index 4.2. Over a median follow-up period of 51.6 months, there was no significant difference in 5-year OS (88.9% vs 77.9%, P = 0.290) and DFS (83.2% vs 75.1%, P = 0.593) between absolute indication (AI) EGC and relative indication (RI) EGC. AI EGC cohort achieved higher en bloc (96.3% vs 87.5%, P = 0.069) and R0 resection rate (93.6% vs 62.5%, P <0.001) when compared to RI EGC. There were no significant differences in SAE (7.3% vs 12.5%, P = 0.363). No mortality or surgical resection ensued from ESD complications. CONCLUSION: ESD safely confers DFS in poor surgical candidates with RI EGC in a large Western cohort. Patients who are elderly and comorbid or decline surgical resection may benefit from ESD and avoid the risks of surgery and its long-term sequelae.

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.

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.

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.

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.

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.).

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.

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.

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 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.