Search

Background:Colorectal cancer is a highly prevalent malignancy and a significant driver of cancer mortality and health-related expenditure worldwide. Polyp removal reduces the incidence and mortality of colorectal cancer. In 2024, endoscopists have an array of resection modalities at their disposal. Each technique requires a unique skillset and has individual advantages and limitations. Consequently, resection in the colorectum requires an evidence-based algorithm approach that considers these factors. Summary:A literature review of endoscopic resection for colonic neoplasia was conducted. Best supporting scientific evidence was summarized for the endoscopic resection of diminutive polyps, large ≥20 mm lesions and polyps containing invasive cancer. Factors including resection modality, complications and lesion selection were explored to inform an algorithm approach to colorectal resection. Key Messages:Endoscopic resection in the colorectum is not a one-size-fits-all approach. Detailed understanding of polyp size, location, morphology and predicted histology are critical factors that inform appropriate endoscopic resection practice.

ObjectiveTo evaluate the risk factors for lymph node metastasis (LNM) after a non-curative (NC) gastric endoscopic submucosal dissection (ESD) and to validate and eventually refine the eCura scoring system in the Western setting. Also, to assess the rate and risk factors for parietal residual disease.DesignRetrospective multicentre multinational study of prospectively collected registries from 19 Western centres. Patients who had been submitted to surgery or had at least one follow-up endoscopy were included. The eCura system was applied to assess its accuracy in the Western setting, and a modified version was created according to the results (W-eCura score). The discriminative capacities of the eCura and W-eCura scores to predict LNM were assessed and compared.ResultsA total of 314 NC gastric ESDs were analysed (72% high-risk resection (HRR); 28% local-risk resection). Among HRR patients submitted to surgery, 25% had parietal disease and 15% had LNM in the surgical specimen. The risk of LNM was significantly different across the eCura groups (areas under the receiver operating characteristic curve (AUC-ROC) of 0.900 (95% CI 0.852 to 0.949)). The AUC-ROC of the W-eCura for LNM (0.916, 95% CI 0.870 to 0.961; p=0.012) was significantly higher compared with the original eCura. Positive vertical margin, lymphatic invasion and younger age were associated with a higher risk of parietal residual lesion in the surgical specimen.ConclusionThe eCura scoring system may be applied in Western countries to stratify the risk of LNM after a gastric HRR. A new score is proposed that may further decrease the number of unnecessary surgeries.

ObjectiveEndoscopic mucosal resection (EMR) is the preferred treatment for non-invasive large (≥20 mm) non-pedunculated colorectal polyps (LNPCPs) but is associated with an early recurrence rate of up to 30%. We evaluated whether standardised EMR training could reduce recurrence rates in Dutch community hospitals.DesignIn this multicentre cluster randomised trial, 59 endoscopists from 30 hospitals were randomly assigned to the intervention group (e-learning and 2-day training including hands-on session) or control group. From April 2019 to August 2021, all consecutive EMR-treated LNPCPs were included. Primary endpoint was recurrence rate after 6 months.ResultsA total of 1412 LNPCPs were included; 699 in the intervention group and 713 in the control group (median size 30 mm vs 30 mm, 45% vs 52% size, morphology, site and access (SMSA) score IV, 64% vs 64% proximal location). Recurrence rates were lower in the intervention group compared with controls (13% vs 25%, OR 0.43; 95% CI 0.23 to 0.78; p=0.005) with similar complication rates (8% vs 9%, OR 0.93; 95% CI 0.64 to 1.36; p=0.720). Recurrences were more often unifocal in the intervention group (92% vs 76%; p=0.006). In sensitivity analysis, the benefit of the intervention on recurrence rate was only observed in the 20–40 mm LNPCPs (5% vs 20% in 20–29 mm, p=0.001; 10% vs 21% in 30–39 mm, p=0.013) but less evident in ≥40 mm LNPCPs (24% vs 31%; p=0.151). In a post hoc analysis, the training effect was maintained in the study group, while in the control group the recurrence rate remained high.ConclusionA compact standardised EMR training for LNPCPs significantly reduced recurrences in community hospitals. This strongly argues for a national dedicated training programme for endoscopists performing EMR of ≥20 mm LNPCPs. Interestingly, in sensitivity analysis, this benefit was limited for LNPCPs ≥40 mm.Trial registration numberNTR7477.

ObjectiveResidual 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.DesignOver 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.Results213 (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.ConclusionsRRA 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 numbersNCT01368289and NCT02000141

Background and aimsGreenhouse gases (GHGs) that trap heat in the atmosphere are composed of carbon dioxide (CO2), methane, nitrous oxide and fluorinated gases (synthetic hydrofluorocarbons, perfluorocarbons and nitrogen trifluoride). In the USA, the health sector accounts for 8.5% of total GHG emissions. The primary objective of this systematic review was to critically analyse the carbon emissions data from GI endoscopic activity.DesignThe GI endoscopy carbon cycle was evaluated at preprocedural, intraprocedural and postprocedural levels. We performed a systematic literature search of articles published on these issues until 30 June 2022 and discussed these available data on endoscopy unit GHG carbon cycle, barriers to reduce GHG emissions and potential solutions. The inclusion criteria were any full-text articles (observational, clinical trials, brief communications, case series and editorials) reporting waste generation from GI endoscopy. Abstracts, news articles and conference proceedings were excluded.ResultsOur search yielded 393 records in PubMed, 1708 in Embase and 24 in Google Scholar. After application of inclusion and exclusion factors, we focused on 9 fulllength articles in detail, only 3 of them were cross-sectional studies (all from the USA), the others reviews or position statements. Therefore, the quality of the studies could not be assessed due to heterogeneity in definitions and amount of emissions.ConclusionsRecognition of carbon emissions generated by GI endoscopy activity is critical. Although multiple limitations exists for quantification of these emission, there is an urgent need for collecting proper data as well as examining novel methods for reduction of these emissions for a sustainable endoscopic practices in the future.

The risk of developing colorectal cancer in patients with chronic kidney disease (CKD) is twice that of the general population, but the factors associated with colorectal cancer are poorly understood. The aim of this study was to identify factors associated with advanced colorectal neoplasia in patients with CKD.

Background and aims: Delayed post-polypectomy bleeding (DPPB) is a commonly described adverse event following polypectomy. Prophylactic clipping may prevent DPPB in some patient subgroups. We performed a meta-analysis to assess both the efficacy and real-world effectiveness of prophylactic clipping. Methods: We performed a database search through March 2020 for clinical trials or observational studies assessing prophylactic clipping and DPPB. Pooled risk ratios (RR) were calculated using random effects models. Subgroup, sensitivity, and meta-regression analyses were performed to elucidate clinical or methodological factors associated with effects on outcomes. Results: A total of 2771 citations were screened, with 11 randomized controlled trials (RCTs) and 9 observational studies included, representing 24,670 colonoscopies. DPPB occurred in 2.0% of patients overall. The pooled RR of DPPB was 0.47 (95% CI 0.29–0.77) from RCTs enrolling only patients with polyps ≥ 20 mm. Remaining pooled RCT data did not demonstrate a benefit for clipping. The pooled RR of DPPB was 0.96 (95% CI 0.61–1.51) from observational studies including all polyp sizes. For patients with proximal polyps of any size, the RR was 0.73 (95% CI 0.33–1.62) from RCTs. Meta-regression confirmed that polyp size ≥ 20 mm significantly influenced the effect of clipping on DPPB. Conclusion: Pooled evidence demonstrates a benefit when clipping polyps measuring ≥ 20 mm, especially in the proximal colon. In lower-risk subgroups, prophylactic clipping likely results in little to no difference in DPPB.

ObjectiveManagement of covert submucosal invasive cancer (SMIC) discovered after piecemeal endoscopic mucosal resection (pEMR) of large (>20 mm) non-pedunculated colorectal polyps is challenging. The residual cancer risk is largely unknown. We sought to evaluate this in a large tertiary referral cohort.DesignCases of covert SMIC following pEMR were identified and followed. Oncological outcomes after surgery were divided based on residual intramural cancer, lymph node metastases (LNM) or both. Risk factors for residual intramural cancer and LNM were analysed based on the original pEMR histological variables. Risk parameters were analysed with respect to low and high-risk variables for residual intramural cancer and LNM.ResultsAmong 3372 cases of large non-pedunculated colorectal polyps, 143 cases of covert SMIC (4.2%) were identified. 109 underwent surgical resection. Histological analysis of pEMR histology was available in 98 of 109 (90%) cases. 62 cases (63%) had no residual malignancy. 36 cases had residual malignancy (residual intramural cancer n=24; LNM n=5; both n=7). All cases of residual intramural cancer could be identified by a R1 histological deep margin. Cases with poor differentiation (PD) and/or lymphovascular invasion (LVI) had a high risk of LNM (12/33), with a very low risk without these criteria (<1%; 0/65). Cases at low risk for LNM with R0 deep margin have a low risk of residual intramural cancer (<1%; 0/35).ConclusionThe majority of cases of large non-pedunculated colorectal polyps with covert SMIC following pEMR will have no residual malignancy. The risk of residual malignancy can be ascertained from three key variables: PD, LVI and R1 deep margin.

ObjectiveEndoscopic 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.DesignStandardised 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.Results88 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).ConclusionFor 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.

Background: Endoscopic papillectomy (EP) is considered a relatively safe and minimally invasive treatment for papillary adenomas. In the literature a significant risk for local recurrence is described. The aim of this study was to evaluate long-term recurrence rates and time-to-recurrence. Additionally, risk factors for recurrence, malignancy and adverse events were studied. Methods: This is a retrospective study in consecutive patients with papillary adenomas who underwent EP in two tertiary referral hospitals between 2001 and 2018. Primary outcome was recurrence in patients with at least 1-year endoscopic follow-up. Secondary outcomes were surgery free survival, adverse events, and mortality within 30 days after the index procedure. Results: A total of 259 patients were found eligible [median age 66 years, 130 male (50.2%)]. Forty-three patients were known with familial adenomatous polyposis (FAP) (16.6%). At least 1-year endoscopic follow-up was available in 154 patients with a total follow-up of 586 person-years and median of 40 months [interquartile range (IQR) 25–75]. Recurrence occurred in 24 cases (15.6%) of which 8 were known with FAP, leading to a recurrence incidence rate of 4.1 per 100 person-years with a median time-to-recurrence of 29 months (IQR 14.75–59.5). Fifty-three patients underwent at least 5-year follow-up, in 6 (11.3%) of them recurrence was encountered after 5 years of which four were known with FAP. No risk factors for recurrence could be identified. Adverse events occurred in 50/259 patients (19.3%). One patient died within 30 days after the procedure. Papillary stenosis occurred in 19/259 (7.3%) of the patients. There were no cases of malignant degeneration during follow-up. Conclusions: Recurrence after EP occurs in a significant proportion of patients and occurs even 5 years after EP. This emphasizes the need for long-term follow-up. We advise to consider at least 5-year follow-up in case of a sporadic adenoma, unless comorbidity makes follow-up clinically irrelevant.

To describe the clinical and procedural outcomes of per‐oral endoscopic myotomy (POEM) for achalasia in Australia. Prospective observational study in three Australian tertiary referral centres, 5 May 2014 – 27 October 2019 (66 months). Patients who had undergone POEM for achalasia. Eckardt scores calculated prior to POEM and six months, one year, and two years after POEM. The primary outcome was clinical success, defined as an Eckardt score of 3 or less without a second intervention. 142 patients underwent POEM for achalasia; their mean age was 52 years (SD, 18 years), 83 were men (58%), and the median length of hospital stay two days (IQR, 1–3 days). Their mean Eckardt score before POEM was 8.0 (SD, 2.4) and 1.1 (SD, 1.6) six months after POEM; it did not change significantly between six months and two years after POEM (mean monthly increase, 0.014 points; 95% CI, –0.001 to 0.029). A total of 127 patients (89%) improved clinically after POEM. Intra‐procedural capnoperitoneum was the only risk factor associated with treatment failure (adjusted hazard ratio, 2.85; 95% CI, 1.08–7.51). Previous treatments — botulinum toxin injection (25 patients, 18%), endoscopic balloon dilatation (69, 49%), and Heller myotomy (14, 10%) — did not affect POEM outcomes. Five patients (4%) experienced major adverse events, including pneumonia, oesophageal leak, empyema and melaena, that were managed during admission and without sequelae. POEM is an effective treatment for achalasia. Significant reductions in Eckardt scores achieved by six months are sustained at two years. POEM can be both a first line definitive therapy and a salvage therapy for patients not helped by other treatments.

ObjectiveLarge (≥20 mm) sessile serrated lesions (L-SSL) are premalignant lesions that require endoscopic removal. Endoscopic mucosal resection (EMR) is the existing standard of care but carries some risk of adverse events including clinically significant post-EMR bleeding and deep mural injury (DMI). The respective risk-effectiveness ratio of piecemeal cold snare polypectomy (p-CSP) in L-SSL management is not fully known.DesignConsecutive patients referred for L-SSL management were treated by p-CSP from April 2016 to January 2020 or by conventional EMR in the preceding period between July 2008 and March 2016 at four Australian tertiary centres. Surveillance colonoscopies were conducted at 6 months (SC1) and 18 months (SC2). Outcomes on technical success, adverse events and recurrence were documented prospectively and then compared retrospectively between the subsequent time periods.ResultsA total of 562 L-SSL in 474 patients were evaluated of which 156 L-SSL in 121 patients were treated by p-CSP and 406 L-SSL in 353 patients by EMR. Technical success was equal in both periods (100.0% (n=156) vs 99.0% (n=402)). No adverse events occurred in p-CSP, whereas delayed bleeding and DMI were encountered in 5.1% (n=18) and 3.4% (n=12) of L-SSL treated by EMR, respectively. Recurrence rates following p-CSP were similar to EMR at 4.3% (n=4) versus 4.6% (n=14) and 2.0% (n=1) versus 1.2% (n=3) for surveillance colonoscopy (SC)1 and SC2, respectively.ConclusionsIn a historical comparison on the endoscopic management of L-SSL, p-CSP is technically equally efficacious to EMR but virtually eliminates the risk of delayed bleeding and perforation. p-CSP should therefore be considered as the new standard of care for L-SSL treatment.

Endoscopic resection (ER) allows optimal staging with potential cure of early-stage luminal malignancies while maintaining organ preservation. ER and surgery are non-competing but complementary therapeutic options. In addition, histological examination of ER specimens can either confirm or refine the pre-procedure diagnosis. ER is used for the treatment of Barrett's related early carcinomas and dysplasias, early-esophageal squamous cell carcinomas and dysplasias, early gastric carcinomas and dysplasia, as well as low-risk submucosal invasive carcinomas (LR-SMIC) and, large laterally spreading adenomas of the colon. For invasive lesions, histological risk factors predict risk of lymph node metastasis and residual disease at the ER site. Important pathological risk factors predictive of lymph node metastasis are depth of tumor invasion, poor differentiation, and lymphovascular invasion. Complete resection with negative margins is critical to avoid local recurrences. For non-invasive lesions, complete resection is curative. Therefore, a systematic approach for handling and assessing ER specimens is recommended to evaluate all above key prognostic features appropriately. Correct handling starts with pinning the specimen before fixation, meticulous macroscopic assessment with orientation of appropriate margins, systematic sectioning, and microscopic assessment of the entire specimen. Microscopic examination should be thorough for accurate assessment of all pathological risk factors and margin assessment. Site-specific issues such as duplication of muscularis mucosa of the esophagus, challenges of assessing ampullectomy specimens and site-specific differences of staging of early carcinomas throughout the gastrointestinal tract (GI) tract should be given special consideration. Finally, a standard, comprehensive pathology report that allows optimal staging with potential cure of early-stage malignancies or better stratification and guidance for additional treatment should be provided.

Endoscopic resection (ER) allows optimal staging with potential cure of early-stage luminal malignancies while maintaining organ preservation. ER and surgery are non-competing but complementary therapeutic options. In addition, histological examination of ER specimens can either confirm or refine the pre-procedure diagnosis. ER is used for the treatment of Barrett's related early carcinomas and dysplasias, early-esophageal squamous cell carcinomas and dysplasias, early gastric carcinomas and dysplasia, as well as low-risk submucosal invasive carcinomas (LR-SMIC) and, large laterally spreading adenomas of the colon. For invasive lesions, histological risk factors predict risk of lymph node metastasis and residual disease at the ER site. Important pathological risk factors predictive of lymph node metastasis are depth of tumor invasion, poor differentiation, and lymphovascular invasion. Complete resection with negative margins is critical to avoid local recurrences. For non-invasive lesions, complete resection is curative. Therefore, a systematic approach for handling and assessing ER specimens is recommended to evaluate all above key prognostic features appropriately. Correct handling starts with pinning the specimen before fixation, meticulous macroscopic assessment with orientation of appropriate margins, systematic sectioning, and microscopic assessment of the entire specimen. Microscopic examination should be thorough for accurate assessment of all pathological risk factors and margin assessment. Site-specific issues such as duplication of muscularis mucosa of the esophagus, challenges of assessing ampullectomy specimens and site-specific differences of staging of early carcinomas throughout the gastrointestinal tract (GI) tract should be given special consideration. Finally, a standard, comprehensive pathology report that allows optimal staging with potential cure of early-stage malignancies or better stratification and guidance for additional treatment should be provided.

Endoscopic tissue resection is a rapidly evolving field. En bloc resection techniques, specifically endoscopic submucosal dissection, allow for organ-sparing curative endoscopic resection for early gastrointestinal cancers. However, using current techniques to quantify depth of invasion, it remains difficult for endoscopists to reliably select optimal endoscopic submucosal dissection candidates. In this review, we highlight that artificial intelligence platforms can now quantify the depth of invasion of esophageal, gastric, and colorectal neoplasia. While real-time performance evaluation is needed, this represents a significant advancement in endoscopic tissue resection and carries the potential to provide real-time guidance for selecting the appropriate tissue resection technique.

The COVID-19 pandemic has had a profound impact on provision of endoscopy services globally as staff and real estate were repurposed. As we begin to recover from the pandemic, a cohesive international approach is needed, and guidance on how to resume endoscopy services safely to avoid unintended harm from diagnostic delays. The aim of these guidelines is to provide consensus recommendations that clinicians can use to facilitate the swift and safe resumption of endoscopy services. An evidence-based literature review was carried out on the various strategies used globally to manage endoscopy during the COVID-19 pandemic and control infection. A modified Delphi process involving international endoscopy experts was used to agree on the consensus statements. A threshold of 80% agreement was used to establish consensus for each statement. 27 of 30 statements achieved consensus after two rounds of voting by 34 experts. The statements were categorised as pre-endoscopy, during endoscopy and postendoscopy addressing relevant areas of practice, such as screening, personal protective equipment, appropriate environments for endoscopy and infection control precautions, particularly in areas of high disease prevalence. Recommendations for testing of patients and for healthcare workers, appropriate locations of donning and doffing areas and social distancing measures before endoscopy are unique and not dealt with by any other guidelines. This international consensus using a modified Delphi method to produce a series of best practice recommendations to aid the safe resumption of endoscopy services globally in the era of COVID-19.

ObjectiveThe optimal approach for removing large laterally spreading lesions at the anorectal junction (ARJ-LSLs) is unknown. Endoscopic mucosal resection (EMR) is a definitive therapy for colorectal LSLs. It is unclear whether it is an effective modality for ARJ-LSLs.DesignEMR outcomes for ARJ-LSLs (distal margin of ≤20 mm from the dentate line) in comparison with rectal LSLs (distal margin of >20 mm from the dentate line) were evaluated within a multicentre observational cohort of LSLs of ≥20 mm. Technical success was defined as the removal of all polypoid tissue during index EMR. Safety was evaluated by the frequencies of intraprocedural bleeding, delayed bleeding, deep mural injury (DMI) and delayed perforation. Long-term efficacy was evaluated by the absence of recurrence (either endoscopic or histologic) at surveillance colonoscopy (SC).ResultsBetween July 2008 and August 2019, 100 ARJ-LSLs and 313 rectal LSLs underwent EMR. ARJ-LSL median size was 40 mm (IQR 35–60 mm). Median follow-up at SC4 was 54 months (IQR 33–83 months). Technical success was 98%. Cancer was present in three (3%). Recurrence occurred in 15.4%, 6.8%, 3.7% and 0% at SC1–SC4, respectively. Among 30 ARJ-LSLs that received margin thermal ablation, no recurrence was identified at SC1 (0.0% vs 25.0%, p=0.002). Technical success, recurrence and adverse events were not different between groups, except for DMI (ARJ-LSLs 0% vs rectal LSLs 4.5%, p=0.027).ConclusionEMR is an effective technique for ARJ-LSLs and should be considered a first-line resection modality for the majority of these lesions.

Endoscopic tissue resection is a rapidly evolving field. En bloc resection techniques, specifically endoscopic submucosal dissection, allow for organ-sparing curative endoscopic resection for early gastrointestinal cancers. However, using current techniques to quantify depth of invasion, it remains difficult for endoscopists to reliably select optimal endoscopic submucosal dissection candidates. In this review, we highlight that artificial intelligence platforms can now quantify the depth of invasion of esophageal, gastric, and colorectal neoplasia. While real-time performance evaluation is needed, this represents a significant advancement in endoscopic tissue resection and carries the potential to provide real-time guidance for selecting the appropriate tissue resection technique.

Endoscopic resection (ER) is the standard of care for the management of large (≥20mm) non-pedunculated colorectal polyps (LNPCP). Certain lesion characteristics increase the risk for incomplete ER, recurrence, harbouring submucosal invasive cancer and post ER adverse events. These include lesion location, morphology, difficult endoscopic access and prior attempts at resection. Such LNPCP are termed ‘complex’. Recognition of complexity is a crucial component of technique selection and resource allocation. Until recently, resection of complex lesions was dominated by surgery. Surgical resection of benign lesions is associated with prolonged hospital stay and post-operative recovery, stoma creation, post-operative complications and even death. Advances in ER techniques have enabled huge strides in the management these lesions and is proven to be safer and more cost-effective than surgery.

Wide-field endoscopic mucosal resection (EMR) is the primary management option for noninvasive laterally spreading colorectal lesions. It has been proved to be safe, highly effective, efficient, and cost-effective. Careful lesion interrogation before resection is essential because it provides essential information, including the risk of submucosal invasive disease. Adjuvant thermal ablation to the post-EMR defect margin has recently been shown to substantially reduce adenoma recurrence. Adenoma recurrence is predictable using the Sydney EMR Recurrence Tool. Adenoma recurrence can be accurately detected using standardized imaging of the post-EMR scar, and can be effectively treated.

ObjectiveTo 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.DesignAn 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.Results1723 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.ConclusionS-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 numberNCT02000141.

Duodenal adenomas are the most common type of polyp arising from the duodenum. These adenomas can occur within and outside of genetic syndromes, and are broadly classified as non-ampullary or ampullary depending on their location. All adenomas have malignant potential and are therefore appropriately treated by endoscopic resection. However, the unique anatomical properties of the duodenum, namely its relatively thin and vascular walls, narrow luminal diameter and relationship to the ampulla and its associated pancreatic and biliary drainage, pose an increased degree of complexity for any endoscopic interventions in this area. This review will discuss the epidemiology of duodenal adenomas, their endoscopic detection and diagnosis, and techniques for safe and effective endoscopic resection of ampullary and non-ampullary lesions.

Background Endoscopic therapy, including by radiofrequency ablation (RFA) or endoscopic mucosal resection (EMR), is first line treatment for Barrett’s esophagus (BE) with high-grade dysplasia (HGD) or intramucosal cancer (IMC) and may be appropriate for some patients with low-grade dysplasia (LGD).Objective The purpose of this study was to investigate the molecular effects of endotherapy.Methods mRNA expression of 16 genes significantly associated with different BE stages was measured in paired pre-treatment BE tissues and post-treatment neo-squamous biopsies from 36 patients treated by RFA (19 patients, 3 IMC, 4 HGD, 12 LGD) or EMR (17 patients, 4 IMC, 13 HGD). EMR was performed prior to RFA in eight patients. Normal squamous esophageal tissues were from 20 control individuals.Results Endoscopic therapy resulted in significant change towards the normal squamous expression profile for all genes. The neo-squamous expression profile was significantly different to the normal control profile for 11 of 16 genes.Conclusion Endotherapy results in marked changes in mRNA expression, with replacement of the disordered BE dysplasia or IMC profile with a more “normal” profile. The neo-squamous mucosa was significantly different to the normal control squamous mucosa for most genes. The significance of this finding is uncertain but it may support continued endoscopic surveillance after successful endotherapy.

Endoscopic therapy, including by radiofrequency ablation (RFA) or endoscopic mucosal resection (EMR), is first line treatment for Barrett’s esophagus (BE) with high-grade dysplasia (HGD) or intramucosal cancer (IMC) and may be appropriate for some patients with low-grade dysplasia (LGD). The purpose of this study was to investigate the molecular effects of endotherapy. mRNA expression of 16 genes significantly associated with different BE stages was measured in paired pre-treatment BE tissues and post-treatment neo-squamous biopsies from 36 patients treated by RFA (19 patients, 3 IMC, 4 HGD, 12 LGD) or EMR (17 patients, 4 IMC, 13 HGD). EMR was performed prior to RFA in eight patients. Normal squamous esophageal tissues were from 20 control individuals. Endoscopic therapy resulted in significant change towards the normal squamous expression profile for all genes. The neo-squamous expression profile was significantly different to the normal control profile for 11 of 16 genes. Endotherapy results in marked changes in mRNA expression, with replacement of the disordered BE dysplasia or IMC profile with a more “normal” profile. The neo-squamous mucosa was significantly different to the normal control squamous mucosa for most genes. The significance of this finding is uncertain but it may support continued endoscopic surveillance after successful endotherapy.

ObjectiveEndoscopic mucosal resection (EMR) is effective for large laterally spreading flat and sessile lesions (LSLs). Sessile serrated adenomas/polyps (SSA/Ps) are linked to the relative failure of colonoscopy to prevent proximal colorectal cancer. We aimed to examine the technical success, adverse events and recurrence following EMR for large SSA/Ps in comparison with large conventional adenomas.DesignOver 74 months till August 2014, prospective multicentre data of LSLs ≥20 mm were analysed. A standardised dye-based conventional EMR technique followed by scheduled surveillance colonoscopy was used.ResultsFrom a total of 2000 lesions, 323 SSA/Ps in 246 patients and 1527 adenomas in 1425 patients were included for analysis. Technical success for EMR was superior in SSA/Ps compared with adenomas (99.1% vs 94.5%, p<0.001). Significant bleeding and perforation were similar in both cohorts. The cumulative recurrence rates for adenomas after 6, 12, 18 and 24 months were 16.1%, 20.4%, 23.4% and 28.4%, respectively. For SSA/Ps, they were 6.3% at 6 months and 7.0% from 12 months onwards (p<0.001). Following multivariable adjustment, the HR of recurrence for adenomas versus SSA/Ps was 1.7 (95% CI 0.9 to 3.0, p=0.097). Subgroup analysis by lesion size revealed an eightfold increased risk of recurrence for 20–25 mm adenomas versus SSA/Ps, but no significantly different risk between lesion types in larger lesion groups.ConclusionRecurrence after EMR of 20–25 mm LSLs is significantly less frequent in SSA/Ps compared with adenomatous lesions. SSA/Ps can be more effectively removed than adenomatous LSLs with equivalent safety. Ensuring complete initial resection is imperative for avoiding recurrence.Trial registration numberClinicalTrials.gov NCT01368289.

ObjectivesPerforation is the most serious complication associated with endoscopic mucosal resection (EMR). We propose a new classification for the appearance and integrity of the muscularis propria (MP) after EMR including various extents of deep mural injury (DMI). Risk factors for these injuries were analysed.DesignEndoscopic images and histological specimens of consecutive patients undergoing EMR of colonic laterally spreading lesions ≥20 mm at a large Australian tertiary referral endoscopy unit were retrospectively analysed using our new DMI classification system. DMI was graded according to MP injury (I/II intact MP without/with fibrosis, III target sign, IV/V obvious transmural perforation without/with contamination). Histological specimens were examined for included MP and patient outcomes were recorded. All type III–V DMI signs were clipped if possible, types I and II DMI were clipped at the endoscopists’ discretion.ResultsEMR was performed in 911 lesions (mean size 37 mm) in 802 patients (male sex 51.4%, mean age 67 years). DMI signs were identified in 83 patients (10.3%). Type III–V DMI was identified in 24 patients (3.0%); clipping was successfully performed in all patients. A clinically significant perforation occurred in two patients (0.2%). Only one of the 59 type I/II cases experienced a delayed perforation. 85.5% of patients with DMI were discharged on the same day, all without sequelae. On multivariable analysis, type III–V DMI was associated with transverse colon location (OR 3.55, p=0.028), en bloc resection (OR 3.84, p=0.005) and high-grade dysplasia or submucosal invasive cancer (OR 2.97, p 0.014).ConclusionsIn this retrospective analysis, use of the new classification and management with clips appeared to be a safe approach. Advanced DMI types (III–V) occurred in 3.0% of patients and were associated with identifiable risk factors. Further prospective clinical studies should use this new classification.Trial registration numberNCT01368289; results.

Endoscopic resection (ER), including endoscopic polypectomy (EP), endoscopic mucosal resection (EMR) and endoscopic submucosal dissection (ESD) are used to remove superficial neoplasms from the colon. Snare resection is used for EP and EMR, whereas endoscopic knives are used to perform dissection in the submucosal space in ESD. 80–90% colonic polyps are <10 millimetres (mm) and are effectively managed by conventional EP. Increasingly cold snare polypectomy is preferred. Large laterally spreading lesions (LSLs) and sessile polyps ≥20 mm are primarily removed by EMR. ESD may be used when superficial invasive disease is suspected and for some LSLs, particularly non-granular subtypes. Resection of colonic lesions by ER is associated with a small but definite incidence of significant complications, most commonly bleeding and perforation. This review discusses complications of ER with a particular focus on their prevention, early recognition and management. In many cases, complications from all three procedures share similar mechanisms and management principles and these are described at the start of each section, followed by a description of specific aspects for individual procedures.

OBJECTIVES:Clinically significant bleeding (CSPEB) is the most frequent adverse event following wide-field endoscopic mucosal resection (WF-EMR) of large sessile and laterally spreading colorectal lesions (LSL). There is limited knowledge regarding accurate prediction of CSPEB. We aimed to derive a score to predict the risk of CSPEB.METHODS:Data on patient and lesion characteristics and outcomes from WF-EMRs of LSL ≥20 mm at 8 referral hospitals were analyzed. The cohort was divided at random into equal sized training and test groups. Independent predictors of CSPEB in the training cohort were identified by multiple logistic regression analysis and used to develop a risk score. The performance of this score was assessed in the independent test cohort.RESULTS:Over 80 months to June 2015, 2,128 patients with 2,424 LSL were referred for WF-EMR. Two thousand and twelve patients were eligible for analysis. There were 135 cases of CSPEB (6.7%). In the training cohort of 1,006 patients, the independent predictors of CSPEB were lesion size >30 mm (odds ratio (OR) 2.5), proximal colonic location (OR 2.3), presence of a major comorbidity (OR 1.5), and epinephrine in injection solution (OR 0.57). The derived risk score comprised lesion size >30 mm (2 points), proximal colon (2 points), presence of major comorbidity (1 point), and absence of epinephrine use (1 point). The probabilities of CSPEB for scores of 0, 1, 2, 3, 4, and ≥5 in the training cohort were 1.5, 2.0, 5.6, 7.8, 9.1, and 17.5% and were 0.9, 6.7, 4.9, 6.2, 9.0, and 15.7% in the test cohort. The probabilities of CSPEB in those with low (score 0–1), medium (score 2–4), and elevated (score 5–6) risk levels were 1.7, 7.1, and 17.5% in the training cohort and 3.4, 6.2, and 15.7% in the test cohort.CONCLUSIONS:Patients at elevated risk of CSPEB can be identified using four readily available variables. This knowledge may improve the management of those undergoing WF-EMR and assist in designing studies evaluating CSPEB.

Most colorectal cancer arises from adenomatous polyps. This gradual process may be interrupted by screening and treatment using colonoscopy and polypectomy. Advances in imaging platforms have led to classification systems that facilitate prediction of histologic type and both stratification for and prediction of the risk of invasion. Endoscopic treatment should be the standard of care even for extensive advanced mucosal neoplasm. Technique selection is influenced by lesion features, location, patient factors, and local expertise. Postprocedural complications are more common following advanced resection and endoscopists should be familiar with risk factors, early detection methods, and management.

Gene silencing in cancer frequently involves hypermethylation and dense nucleosome occupancy across promoter regions. How a promoter transitions to this silent state is unclear. Using colorectal adenomas, we investigated nucleosome positioning, DNA methylation, and gene expression in the early stages of gene silencing. Genome-wide gene expression correlated with highly positioned nucleosomes upstream and downstream of a nucleosome-depleted transcription start site (TSS). Hypermethylated promoters displayed increased nucleosome occupancy, specifically at the TSS. We investigated 2 genes, CDH1and CDKN2B, which were silenced in adenomas but lacked promoter hypermethylation. Instead, silencing correlated with loss of nucleosomes from the -2 position upstream of the TSS relative to normal mucosa. In contrast, permanent CDH1silencing in carcinoma cells was characterized by promoter hypermethylation and dense nucleosome occupancy. Our findings suggest that silenced genes transition through an intermediary stage involving altered promoter nucleosome positioning, before permanent silencing by hypermethylation and dense nucleosome occupancy.

In mouse models, loss of the candidate tumor suppressor gene Ubiquitin Specific Protease 44 (USP44) is associated with aneuploidy and cancer. USP44is also transcriptionally silenced in human cancers. Here we investigated the molecular mechanism of USP44silencing and whether this correlated with aneuploidy in colorectal adenomas. DNA methylation at the USP44CpG island (CGI) promoter was measured using combined bisulfite restriction analysis (COBRA) in colorectal cancer (CRC) cell lines (n = 18), and with COBRA and bisulfite sequencing in colorectal adenomas (n = 89) and matched normal colonic mucosa (n = 51). The USP44CGI was hypermethylated in all CRC cell lines, in most colorectal adenomas (79 of 89, 89%) but rarely in normal mucosa samples (3 of 51, 6%). USP44expression was also compared between normal mucosa and paired hypermethylated adenomas in six patients using qRT-PCR. Hypermethylation of the USP44CGI in adenomas was associated with a 1.8 to 5.5-fold reduction in expression compared with paired normal mucosa. Treatment of CRC cell lines with the DNA hypomethylating agent decitabine resulted in a 14 to 270-fold increase in USP44expression. Whole genome SNP array data showed that gain or loss of individual chromosomes occurred in adenomas, but hypermethylation did not correlate with more aneuploidy. In summary, our data shows that USP44is epigenetically inactivated in colorectal adenomas, but this alone is not sufficient to cause aneuploidy in colorectal neoplasia.

Background:“Sphincterotomy stenosis” is a recognized late complication of endoscopic biliary sphincterotomy. The narrowing is limited to the biliary orifice and can be managed simply by repeat sphincterotomy. A similar but poorly characterized post-sphincterotomy complication involves narrowing that extends from the biliary orifice for a variable distance along the bile duct, beyond the duodenal wall. This lesion cannot be managed by repeating the sphincterotomy. Methods:Six patients (3 men) are described with sphincterotomy associated biliary strictures, all smooth and high grade, presenting at a median of 19 months (range 8 to 60 months) after sphincterotomy. Further sphincterotomy was not possible as an intra-duodenal segment of bile duct was no longer visible. Endoscopic management consisted of serial incremental stent exchange at 2- to 4-month intervals. The goal of therapy was to place two 11.5F stents side-by-side. Results:Stricture resolution was documented by cholangiography in all patients. One patient with a stricture resistant to treatment required three 10F stents side-by-side, and another underwent treatment to a maximum of adjacent 11.5F and 7F stents. Two 11.5F stents were eventually placed in the other four patients. Overall median duration of stent placement was 12.5 months. At a median of 26.5 months of stent-free follow-up, all patients remain asymptomatic. Conclusion:Sphincterotomy-associated biliary strictures are a distinct late complication of biliary sphincterotomy. These recalcitrant lesions are not amenable to repeat sphincterotomy; however, the results of this study suggest that they may be managed successfully by serial placement of stents of incrementally increasing diameter. (Gastrointest Endosc 2000;52:494-9).

Background:In patients with hepatic metastases from colorectal carcinoma there is a distinct subgroup in whom jaundice is not due to hepatic replacement but rather biliary obstruction. We reviewed our experience with stent insertion in patients with malignant proximal biliary obstruction from metastatic colorectal carcinoma. Methods:Thirty-three patients were treated between July 1992 and December 1996. Placement of a single stent was attempted at initial endoscopic retrograde cholangiopancreatography. Hilar biliary obstruction was classified according to Bismuth's classification. Results:Successful stent placement was possible in 94% overall and at initial endoscopic retrograde cholangiopancreatography in 39% of patients. Successful stent placement occurred significantly more often in patients with a type I stricture. Cholangitis was the principal complication occurring in 24% of patients. The 30-day mortality rate was 24%, with death occurring significantly less often in patients with a type I or II stricture. Overall, 45% of patients had a 30% fall in bilirubin at 1 week. The median survival was 81 days, with significantly longer survival seen in patients with a type I or II stricture. Conclusions:Endoscopic stent placement offers effective palliation in most patients with hilar obstruction from colorectal metastases. A subset of patients with type III strictures and greater than 3 intrahepatic metastases often do not benefit from stent insertion. (Gastrointest Endosc 2000;51:412-7.)

Background:Nd:YAG laser therapy has been shown to be highly effective in the palliation of dysphagia due to inoperable esophageal malignancy. However, the duration of response and the degree of palliation present at death have not been adequately addressed. Methods:Seventy consecutive patients with inoperable malignant dysphagia (mean age, 70 years; 48 men, 22 women) underwent palliative laser therapy. Dysphagia was assessed on a 5-point scale (0, normal; 4, complete dysphagia) before and after laser therapy and within 2 weeks of death. Results:Ninety-six percent of patients were palliated initially (70% successful, 26% partial). Mean swallowing score improved from 2.3 to 1.1 (p< 0.001) with a mean of 1.9 initial treatment sessions. Swallowing score remained improved in the last two weeks of life at a mean of 1.7 (p< 0.001). Seventy-three percent of patients were palliated at death (36% successful, 37% partial); median survival was six months. The mean total number of laser sessions was 3.4, with a mean time interval between laser sessions of 27.2 days. Complications included one perforation (1.4%) resulting in death. Conclusion:Endoscopic laser therapy provides safe and effective initial palliation of inoperable malignant dysphagia. In the majority of patients the palliation is maintained until death. (Gastrointest Endosc 1996;43:29-32.)

This article reviews the current and future applications of peroral endoscopic choledochoscopy. As endoscopic technology has evolved with smaller, more durable miniscopes, the range of diagnostic and therapeutic uses has increased proportionately. The success of intraductal lithotripsy coupled with the advent of miniscopes that can be used through standard duodenoscopes will enable most endoscopists to remove almost all bile duct stones. Similarly, the accuracy of tissue sampling and tumor staging will be enhanced. The clinical impact of these developments are reviewed.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.