Yield of capsule endoscopy and subsequent device-assisted enteroscopy: Experience at an Australian tertiary centre.

BACKGROUND: Small bowel capsule endoscopy (SBCE) and device-assisted enteroscopy (DAE) have an established role in the investigation and management of small bowel pathology. Previous studies have reported on the yield of SBCE (60%) and DAE (57%), but none have been in an Australian setting. AIMS: To determine the yield of SBCE and any DAE performed as a direct consequence of SBCE in an Australian referral centre. METHODS: A single-centre retrospective study was conducted at a tertiary hospital in Australia, enrolling consecutive patients between 1 January 2009 and 31 December 2021 undergoing SBCE. Data were collected with respect to demographics, procedural factors and findings, as well as findings and interventions of any DAE procedures performed after the SBCE. RESULTS: 1214 SBCEs were performed, with a median age of 66 years old (60.8% men). The predominant indications were anaemia (n = 853, 70.2%) and overt gastrointestinal bleeding (n = 320, 26.4%). Of the complete small bowel studies (1132/1214, 93.2%), abnormal findings were detected in 588 cases (51.9%), most commonly angioectasias (266/588, 45.2%), erosions (106/588, 18.0%) and ulcers (97/588, 8.6%). 165 patients underwent a DAE (117 antegrade, 48 retrograde). Antegrade DAE had a higher yield than retrograde DAE (77.8% vs 54.2%; P = 0.002) and a higher rate of intervention (69.2% vs 37.5%; P < 0.001). CONCLUSION: In this largest single-centre cohort of patients undergoing SBCE to date, there is a similar yield of abnormal findings compared to existing literature. DAE, especially with an antegrade approach, had high diagnostic and therapeutic yield when pursued after a positive SBCE study.

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.

Effectiveness and safety of cold snare polypectomy and cold endoscopic mucosal resection for nonpedunculated colorectal polyps of 10-19 mm: a multicenter observational cohort study.

BACKGROUND : Cold snare polypectomy (CSP) is the standard of care for the resection of small (< 10 mm) colonic polyps. Limited data exist for its efficacy for medium-sized (10-19 mm) nonpedunculated polyps, especially conventional adenomas. This study evaluated the effectiveness and safety of CSP/cold endoscopic mucosal resection (C-EMR) for medium-sized nonpedunculated colonic polyps. METHODS : A prospective multicenter observational study was conducted of all morphologically suitable nonpedunculated colonic polyps of 10-19 mm removed by CSP/C-EMR between May 2018 and June 2021. Once resection was complete, multiple biopsies were taken of the margins circumferentially and centrally. The primary outcome was the incomplete resection rate (IRR), based on residual polyp in these biopsy specimens. Secondary outcomes were recurrence rate at first surveillance colonoscopy and rates of adverse events (AEs). RESULTS : CSP/C-EMR was performed for 350 polyps (median size 15 mm; 266 [76.0 %] Paris 0-IIa classification) in 295 patients. Submucosal injection was used for 87.1 % (n = 305) of polyps. Histology showed 68.6 % adenomas, 26.0 % sessile serrated lesions (SSLs) without dysplasia, 4.0 % SSL with dysplasia, and 1.4 % hyperplastic polyps. The IRRs based on margin or central biopsies being positive were 1.7 % (n = 6) and 0.3 % (n = 1), respectively. The polyp recurrence rate was 1.7 % (n = 4) at first surveillance colonoscopy - completed for 65.4 % (n = 229) of polyps at a median interval of 9.7 months. AEs occurred in 3.4 % (n = 10) of patients: four with post-polypectomy pain; three self-limiting post-polypectomy bleeds; two post-polypectomy-syndrome-like presentations; and one intraprocedural bleed treated with clips. There were no perforations. CONCLUSION : CSP/C-EMR for morphologically suitable nonpedunculated colonic polyps of 10-19 mm is effective and safe, including for conventional adenomas. Rates of incomplete resection and recurrence were low, with few AEs. Studies directly comparing this method with hot snare resection are required.

Higher power short duration vs. lower power longer duration posterior wall ablation for atrial fibrillation and oesophageal injury outcomes: a prospective multi-centre randomized controlled study (Hi-Lo HEAT trial).

AIMS: Radiofrequency (RF) ablation for pulmonary vein isolation (PVI) in atrial fibrillation (AF) is associated with the risk of oesophageal thermal injury (ETI). Higher power short duration (HPSD) ablation results in preferential local resistive heating over distal conductive heating. Although HPSD has become increasingly common, no randomized study has compared ETI risk with conventional lower power longer duration (LPLD) ablation. This study aims to compare HPSD vs. LPLD ablation on ETI risk. METHODS AND RESULTS: Eighty-eight patients were randomized 1:1 to HPSD or LPLD posterior wall (PW) ablation. Posterior wall ablation was 40 W (HPSD group) or 25 W (LPLD group), with target AI (ablation index) 400/LSI (lesion size index) 4. Anterior wall ablation was 40-50 W, with a target AI 500-550/LSI 5-5.5. Endoscopy was performed on Day 1. The primary endpoint was ETI incidence. The mean age was 61 ± 9 years (31% females). The incidence of ETI (superficial ulcers n = 4) was 4.5%, with equal occurrence in HPSD and LPLD (P = 1.0). There was no difference in the median value of maximal oesophageal temperature (HPSD 38.6°C vs. LPLD 38.7°C, P = 0.43), or the median number of lesions per patient with temperature rise above 39°C (HPSD 1.5 vs. LPLD 2, P = 0.93). Radiofrequency ablation time (23.8 vs. 29.7 min, P < 0.01), PVI duration (46.5 vs. 59 min, P = 0.01), and procedure duration (133 vs. 150 min, P = 0.05) were reduced in HPSD. After a median follow-up of 12 months, AF recurrence was lower in HPSD (15.9% vs. LPLD 34.1%; hazard ratio 0.42, log-rank P = 0.04). CONCLUSION: Higher power short duration ablation was associated with similarly low rates of ETI and shorter total/PVI RF ablation times when compared with LPLD ablation. Higher power short duration ablation is a safe and efficacious approach to PVI.

Oncological outcomes after piecemeal endoscopic mucosal resection of large non-pedunculated colorectal polyps with covert submucosal invasive cancer.

OBJECTIVE: Management 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. DESIGN: Cases 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. RESULTS: Among 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). CONCLUSION: The 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.

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.

Clinical utility of purgative bowel preparation before capsule endoscopy: a multicenter, blinded, randomized controlled trial.

BACKGROUND AND AIMS: Optimal bowel preparation before capsule endoscopy (CE) is currently unknown. In this multicenter, blinded, randomized controlled trial, we assessed clinical effectiveness of 2 types of purgative regimen and a control arm of clear fluid only. METHODS: Patients with suspected small intestinal bleeding were randomized into 3 arms: arm A, clear fluids only for 18 hours before CE and simethicone 200 mg in 150 mL water immediately before CE; arm B, same as A + 2 L of polyethylene glycol (PEG) 12 hours before CE; and arm C, same as A + 1 L PEG + sodium ascorbate 3 hours before CE. To assess diagnostic yield, lesions were classified either as highly relevant (P2) or less relevant (P0 or P1) lesions. Small-bowel visualization quality (SBVQ) was assessed using the Brotz score. Patient tolerability was assessed using the visual analog scale (0-10, with lower scores indicating better tolerability). RESULTS: Two hundred twenty-nine patients completed the study. The mean age was 58.7 years (95% confidence interval, 29.3-87.9), and 47.2% were men. There was no significant difference in diagnosis of P2 lesions in arms A, B, and C (48.7%, 48.0%, and 45.9%, respectively; P = .94). Overall SBVQ and distal SBVQ were similar across the 3 arms (P = .94 and P = .68, respectively). Patients reported better tolerability in arm A (mean score, 1.5) compared with arms B and C (mean score, 3.5 and 2.6, respectively; P < .001). CONCLUSIONS: The use of a purgative bowel preparation before CE does not improve diagnostic yield or small-bowel visualization and is associated with lower patient tolerance. (Clinical trial registration number: ACTRN 12614000883617.).

Critical peptic ulcer bleeding requiring massive blood transfusion: outcomes of 270 cases.

BACKGROUND: Critical peptic ulcer bleeding requiring massive transfusion is a gastroenterological emergency. Few data exist on management and outcomes. The Australian and New Zealand Massive Transfusion Registry collects comprehensive data on adult patients receiving massive transfusion across all bleeding contexts. AIM: To evaluate clinical factors, management (procedural interventions, transfusions) and outcomes after massive transfusion for critical peptic ulcer bleeding. METHOD: Demographics, diagnosis, procedures and mortality data were available for 5482 massive transfusion cases from 23 hospitals. International Classification of Diseases 10th Edition, Australian Modification codes were used to determine peptic ulcer bleeding and the Australian Classification of Health Intervention for interventions (i.e. endoscopic, radiological, surgical). RESULTS: Peptic ulcer bleeding accounted for 270 (4.9%) of all in-hospital massive transfusion cases; 70% were male. Median number of red blood cell (RBC) units transfused was 7 (interquartile range, 6-10). Thirty-day mortality was 19.6%. Age (75 vs 67 years; P = 0.009) and Charlson Comorbidity Index (3 vs 1; P < 0.001) were higher in those who died. Highest 24-h international normalised ratio (1.5 vs 1.4; P < 0.001) and creatinine (118 µmol/L vs 96 µmol/L; P = 0.03) and nadir platelet count (86 × 109 /L vs 118 × 109 /L; P = 0.01) were also associated with 30-day mortality. There were no differences in mortality according to number of RBC, platelets or plasma units transfused, gastroscopy (with or without intervention), interventional radiology or surgery. CONCLUSION: One in five patients with critical peptic ulcer bleeding requiring massive transfusion died by 30 days. Mortality was associated with patient characteristics rather than clinical interventions (e.g. procedures, blood product transfusion).

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

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

Cold snare piecemeal EMR of large sessile colonic polyps ≥20 mm (with video).

BACKGROUND AND AIMS: Conventional EMR using a hot snare is the standard of care for resection of large (≥20 mm) nonmalignant sessile colonic polyps. Serious adverse events are predominantly because of electrocautery. This could potentially be avoided by cold snare piecemeal EMR (CSP-EMR). This study aimed to evaluate the safety and efficacy of CSP-EMR of sessile colonic polyps sized ≥20 mm. METHODS: All cases of CSP-EMR at 5 Australian academic hospitals for sessile polyps ≥20 mm over a 2-year period, from January 2016 to December 2017, were identified retrospectively. Efficacy was defined as the absence of residual or recurrent polyp tissue during the first surveillance colonoscopy (SC1) and second surveillance colonoscopy (SC2). Clinically significant intraprocedural or delayed adverse events and surveillance colonoscopy findings were assessed by reviewing medical records. RESULTS: CSP-EMR was performed on 204 polyps sized ≥20 mm in 186 patients (men, 33.8%; median age, 68 years). SC1 for 164 polyps (80.4%) at a median interval of 150 days showed residual or recurrent polyp in 9 cases (5.5%; 95% confidence interval, 3%-11%). SC2 for 113 polyps (72.9%) at a median interval of 18 months showed late residual or recurrent polyp in 4 cases (3.5%; 95% confidence interval, .9%-8.5%) after a normal SC1. Intraprocedural bleeding was successfully treated in 4 patients (2.2%), whereas 7 patients (3.8%) experienced self-limited clinically significant post-EMR bleeding and 1 patient (.5%) required overnight observation for nonspecific abdominal pain that resolved spontaneously. None experienced other adverse events. CONCLUSIONS: CSP-EMR of sessile colonic polyps ≥20 mm is technically feasible, effective, and safe. The adverse event rate and polyp recurrence rate were low. Randomized or large prospective trials are required to confirm the noninferiority and improved safety of CSP-EMR compared with conventional EMR and to further determine the polyp morphologies that are best suited for CSP-EMR.

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

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

Clinical coding data algorithm to categorize type of gastrointestinal bleeding as a primary reason for massive transfusion: results from the Australian and New Zealand Massive Transfusion Registry.

BACKGROUND: Management of major gastrointestinal bleeding (GIB) may require massive transfusion (MT), but limited data are available. Upper and lower GIB have different aetiologies, prognosis, bleeding patterns and outcomes. Better understanding of current transfusion management and outcomes in these patients is important. We sought to define and validate an algorithm based on clinical coding data to distinguish critical upper and lower GIB using data from the Australian and New Zealand Massive Transfusion Registry (ANZ-MTR). STUDY DESIGN AND METHODS: Australian and New Zealand Massive Transfusion Registry hospital-source data on adult patients receiving a MT (defined as ≥5 red cell units within 4 h) for any bleeding context were used. An algorithm allocating ICD-10-AM codes into 'probable' or 'possible' causes of GIB was developed and applied to the ANZ-MTR. Source medical records of 69 randomly selected cases were independently reviewed to validate the algorithm. RESULTS: Of 5482 MT cases available from 25 hospitals, 716 (13%) were identified as GIB with 538/716 (75%) categorized 'probable' and 178/716 'possible' GIB. Upper and lower GIB causes of MT were identified for 455/538 (85%) and 76/538 (14%) 'probable' cases, respectively; 7/538 (1·3%) cases had both upper and lower GIB. Allocation by the algorithm into a 'probable' GIB category had a 95·7% (CI: 90-100%) positive predictive value when validated against source medical records. CONCLUSION: An algorithm based on ICD-10-AM codes can be used to accurately categorize patients with luminal GIB as the primary reason for MT, enabling further study of this critically unwell and resource-intensive cohort of patients.

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

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

The size, morphology, site, and access score predicts critical outcomes of endoscopic mucosal resection in the colon.

BACKGROUND: The SMSA (size, morphology, site, access) polyp scoring system is a method of stratifying the difficulty of polypectomy through assessment of four domains. The aim of this study was to evaluate the ability of SMSA to predict critical outcomes of endoscopic mucosal resection (EMR). METHODS: We retrospectively applied SMSA to a prospectively collected multicenter database of large colonic laterally spreading lesions (LSLs) ≥ 20 mm referred for EMR. Standard inject-and-resect EMR procedures were performed. The primary end points were correlation of SMSA level with technical success, adverse events, and endoscopic recurrence. RESULTS: 2675 lesions in 2675 patients (52.6 % male) underwent EMR. Failed single-session EMR occurred in 124 LSLs (4.6 %) and was predicted by the SMSA score (P < 0.001). Intraprocedural and clinically significant postendoscopic bleeding was significantly less common for SMSA 2 LSLs (odds ratio [OR] 0.36, P < 0.001 and OR 0.23, P < 0.01) and SMSA 3 LSLs (OR 0.41, P  < 0.001 and OR 0.60, P = 0.05) compared with SMSA 4 lesions. Similarly, endoscopic recurrence at first surveillance was less likely among SMSA 2 (OR 0.19, P < 0.001) and SMSA 3 (OR 0.33, P < 0.001) lesions compared with SMSA 4 lesions. This also extended to second surveillance among SMSA 4 LSLs. CONCLUSION: SMSA is a simple, readily applicable, clinical score that identifies a subgroup of patients who are at increased risk of failed EMR, adverse events, and adenoma recurrence at surveillance colonoscopy. This information may be useful for improving informed consent, planning endoscopy lists, and developing quality control measures for practitioners of EMR, with potential implications for EMR benchmarking and training.

Endoscopic mucosal resection for large serrated lesions in comparison with adenomas: a prospective multicentre study of 2000 lesions.

OBJECTIVE: Endoscopic 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. DESIGN: Over 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. RESULTS: From 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. CONCLUSION: Recurrence 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 NUMBER: ClinicalTrials.gov NCT01368289.

Role of capsule endoscopy and fecal biomarkers in small-bowel Crohn's disease to assess remission and predict relapse.

BACKGROUND AND AIMS: Capsule endoscopy (CE) is the most sensitive test to diagnose small-bowel Crohn's disease (CD). Conventional parameters poorly assess CD remission, and although fecal biomarkers assess colonic activity, their role in assessing remission is uncertain. We report CE findings in small-bowel CD patients in clinical remission compared with fecal biomarkers and standard clinical tools to determine mucosal remission and predict relapses. METHODS: Forty-three adult small-bowel CD patients in clinical remission (Crohn's Disease Activity Index [CDAI] <150) were prospectively enrolled at 4 academic centers and followed clinically for 12 months. Baseline CE studies were scored using the Capsule Endoscopy Scoring Index (CESI or Lewis score). Baseline and endpoint fecal biomarkers were assayed. RESULTS: CE findings were normal in 17 patients (40%), mild inflammation in 19 (44%), and moderate to severe inflammation in 7 (16%). Of the 26 patients (60%) with mucosal inflammation on CE, 85% had elevated baseline fecal calprotectin and 77% elevated lactoferrin level. Calprotectin and lactoferrin were normal in all patients without inflammation and elevated in all with moderate to severe inflammation. CESI correlated significantly with calprotectin, lactoferrin, and S100A12 levels but not either CDAI or C-reactive protein. During follow-up, 14% of patients exhibited a clinical flare; all had mucosal inflammation at CE and 83% had elevated baseline calprotectin and lactoferrin levels. CONCLUSIONS: In small-bowel CD patients in clinical remission, many had ongoing mucosal inflammation assessed by CE and fecal biomarkers. Only some developed a clinical flare during medium-term follow-up. These findings suggest CE and fecal biomarkers are useful in monitoring small-bowel CD progress.

Adenoma recurrence after piecemeal colonic EMR is predictable: the Sydney EMR recurrence tool.

BACKGROUND AND AIMS: EMR is the primary treatment of large laterally spreading lesions (LSLs) in the colon. Residual or recurrent adenoma (RRA) is a major limitation. We aimed to identify a robust method to stratify the risk of RRA. METHODS: Prospective multicenter data on consecutive LSLs ≥20 mm removed by piecemeal EMR from 8 Australian tertiary-care centers were included (September 2008 until May 2016). A logistic regression model for endoscopically determined recurrence (EDR) was created on a randomly selected half of the cohort to yield the Sydney EMR recurrence tool (SERT), a 4-point score to stratify the incidence of RRA based on characteristics of the index EMR. SERT was validated on the remainder of the cohort. RESULTS: Analysis was performed on 1178 lesions that underwent first surveillance colonoscopy (SC1) (median 4.9 months, interquartile range [IQR] 4.9-6.2). EDR was detected in 228 of 1178 (19.4%) patients. LSL size ≥40 mm (odds ratio [OR] 2.47; P < .001), bleeding during the procedure (OR 1.78; P = .024), and high-grade dysplasia (OR 1.72; P = .029) were identified as independent predictors of EDR and allocated scores of 2, 1, and 1, respectively to create SERT. Lesions with SERT scores of 0 (SERT = 0) had a negative predictive value of 91.3% for RRA at SC1, and SERT was shown to stratify RRA to specific follow-up intervals by using Kaplan Meier curves (log-rank P < .001). CONCLUSIONS: Guidelines recommend SC1 within 6 months of EMR. SERT accurately stratifies the incidence of RRA after EMR. SERT = 0 lesions could safely undergo first surveillance at 18 months, whereas lesions with SERT scores between 1 and 4 (SERT 1-4) require surveillance at 6 and 18 months. (Clinical trial registration number: NCT01368289.).

Clinical and endoscopic predictors of cytological dysplasia or cancer in a prospective multicentre study of large sessile serrated adenomas/polyps.

OBJECTIVE: The serrated neoplasia pathway accounts for up to 30% of all sporadic colorectal cancers (CRCs). Sessile serrated adenomas/polyps (SSA/Ps) with cytological dysplasia (SSA/P-D) are a high-risk serrated CRC precursor with little existing data. We aimed to describe the clinical and endoscopic predictors of SSA/P-D and high grade dysplasia (HGD) or cancer. DESIGN: Prospective multicentre data of SSA/Ps ≥20 mm referred for treatment by endoscopic mucosal resection (September 2008-July 2013) were analysed. Imaging and lesion assessment was standardised. Histological findings were correlated with clinical and endoscopic findings. RESULTS: 268 SSA/Ps were found in 207/1546 patients (13.4%). SSA/P-D comprised 32.4% of SSA/Ps ≥20 mm. Cancer occurred in 3.9%. On multivariable analysis, SSA/P-D was associated with increasing age (OR=1.69 per decade; 95% CI (1.19 to 2.40), p0.004) and increasing lesion size (OR=1.90 per 10 mm; 95% CI (1.30 to 2.78), p0.001), an 'adenomatous' pit pattern (Kudo III, IV or V) (OR=3.98; 95% CI (1.94 to 8.15), p<0.001) and any 0-Is component within a SSA/P (OR=3.10; 95% CI (1.19 to 8.12) p0.021). Conventional type dysplasia was more likely to exhibit an adenomatous pit pattern than serrated dysplasia. HGD or cancer was present in 7.2% and on multivariable analysis, was associated with increasing age (OR=2.0 per decade; 95% CI 1.13 to 3.56) p0.017) and any Paris 0-Is component (OR=10.2; 95% CI 3.18 to 32.4, p<0.001). CONCLUSIONS: Simple assessment tools allow endoscopists to predict SSA/P-D or HGD/cancer in SSA/Ps ≥20 mm. Correct prediction is limited by failure to recognise SSA/P-D which may mimic conventional adenoma. Understanding the concept of SSA/P-D and the pitfalls of SSA/P assessment may improve detection, recognition and resection and potentially reduce interval cancer. TRIAL REGISTRATION NUMBER: NCT01368289.

Cost Analysis of Endoscopic Mucosal Resection vs Surgery for Large Laterally Spreading Colorectal Lesions.

BACKGROUND & AIMS: Large laterally spreading lesions (LSL) in the colon and rectum can be safely and effectively removed by endoscopic mucosal resection (EMR). However, many patients still undergo surgery. Endoscopic treatment may be more cost effective. We compared the costs of endoscopic versus surgical management of large LSL. METHODS: We performed a prospective, observational, multicenter study of consecutive patients referred to 1 of 7 academic hospitals in Australia for the management of large LSL (≥ 20 mm) from January 2010 to December 2013. We collected data on numbers of patients undergoing EMR, actual endoscopic management costs (index colonoscopy, hospital stay, adverse events, and first surveillance colonoscopy), characteristics of patients and lesions, outcomes, and adverse events, and findings from follow-up examinations 14 days, 4-6 months, and 16-18 months after treatment. We compared data from patients who underwent EMR with those from a model in which all patients underwent surgery without any complications. Event-specific costs, based on Australian refined diagnosis-related group codes, were used to estimate average cost per patient. RESULTS: EMR was performed on 1489 lesions (mean size, 36 mm) in 1353 patients (mean age, 67 years; 52.1% male). Total costs involved in the endoscopic management of large LSL were US $6,316,593 and total inpatient hospitalization length of stay was 1180 days. The total cost predicted for the surgical management group was US $16,601,502, with a total inpatient hospitalization length of stay of 4986 days. Endoscopic management produced a potential total cost saving of US $10,284,909; the mean cost difference per patient was US $7602 (95% confidence interval, $8458-$9220; P < .001). Inpatient hospitalization length of stay was reduced by 2.81 nights per patient (95% confidence interval, 2.69-2.94; P < .001). CONCLUSIONS: In a large multicenter study, endoscopic management of large LSL by EMR was significantly more cost-effective than surgery. Endoscopic management by EMR at an appropriately experienced and resourced tertiary center should be considered the first line of therapy for most patients with this disorder. This approach is likely to deliver substantial overall health expenditure savings. ClinicalTrials.gov, Number: NCT01368289.

Prediction of Clinically Significant Bleeding Following Wide-Field Endoscopic Resection of Large Sessile and Laterally Spreading Colorectal Lesions: A Clinical Risk Score.

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.