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.

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.

Drainage of pancreatic fluid collections using a lumen-apposing metal stent with an electrocautery-enhanced delivery system.

BACKGROUND AND AIM: Our aim was to evaluate the efficacy and safety of a lumen-apposing metal stent with an electrocautery-enhanced delivery system (EDS-LAMS) for endoscopic ultrasound (EUS)-guided drainage of pancreatic fluid collections (PFCs) in regular clinical practice. METHODS: A retrospective and subsequent prospective analysis was undertaken of all patients who underwent EUS-guided drainage of their PFCs using the EDS-LAMS at 17 tertiary therapeutic endoscopy centers. RESULTS: Two hundred eight cases of EDS-LAMS deployment were attempted in 202 patients (mean age 52.9 years) at time of evaluation. Ninety-seven patients had pancreatic pseudocysts (PPs), 75 walled-off pancreatic necrosis (WOPN), 10 acute peripancreatic fluid collections (APFCs), 6 acute necrotic collections (ANCs), and 14 postoperative collections (POCs). Procedural technical success was achieved in 202/208 cases (97.1%). Maldeployment occurred in 7/208 cases (3.4%). Clinical success was achieved in 142/160 (88.8%) patients (PP 90%, WOPN 85.2%, APFC 100%, ANC 75%, POC 100%). Delayed adverse events included stent migration in 15/202 (7.4%), stent occlusion and infection in 16/202 (7.9%), major bleeding in 4/202 (2%), and buried EDS-LAMS in 2/202 (1%). PFC recurrence occurred in 13/142 (9.2%) patients; 9/202 (4.5%) required surgical or radiological intervention for PFC management after EDS-LAMS insertion. CONCLUSIONS: This large international multicenter study evaluating the EDS-LAMS for drainage of PFCs in routine clinical practice suggests that the EDS-LAMS are safe and effective for drainage of all types of PFCs; however, further endoscopic therapy is often required for WOPN. Major bleeding was a rare complication in our cohort.

Complications of cold versus hot snare polypectomy of 10-20 mm polyps: A retrospective cohort study.

BACKGROUND AND AIM: Cold snare polypectomy is safe and efficacious for removing polyps <10 mm with reduced rates of delayed postpolypectomy bleeding and postpolypectomy syndrome. This technique can also be used for sessile polyps ≥10 mm; however, further evidence is required to establish its safety. The aim of this study was to compare intraprocedure and postprocedure adverse events in patients who underwent cold (CSP) versus hot snare polypectomy (HSP) of 10-20 mm sessile colonic polyps. METHODS: Electronic medical records and endoscopy reports of all patients who underwent polypectomy for Paris 0-IIa, Is, or 0-IIa + Is 10-20 mm colonic polyps between January 2015 and June 2017 at three tertiary academic hospitals and one private hospital were retrospectively reviewed. Data on patient demographics, polyp characteristics, method of polypectomy, and intraprocedural and postpolypectomy adverse events were collected. RESULTS: A total of 408 patients (median age 67, 50% male) had 604 polyps, 10-20 mm in size, removed. Of these, 258 polyps were removed by HSP, with a median size of 15 mm (interquartile range [IQR] 12-20), compared to 346 polyps that were removed by CSP, with median size of 12 mm (IQR 10-15), P < 0.001. In the HSP group, 15 patients presented with postprocedure complications, including 11 with clinically significant bleeding, 2 with postpolypectomy syndrome, and 2 with abdominal pain. This compares with no postpolypectomy complications in the CSP group, P < 0.001. CONCLUSION: In this study, CSP was not associated with any postpolypectomy adverse events. CSP appears to be safer than HSP for removing 10-20 mm-sized sessile polyps. A prospective multicenter study has been commenced to verify these findings and to assess the efficacy of CSP for the complete resection of polyps of this size.

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.

Augmentation with pre-emptive macrogol-based osmotic laxative does not significantly improve standard bowel preparation in unselected patients: A randomized trial.

BACKGROUND AND AIM: The addition of a laxative prior to a standard bowel preparation (BP) has shown variable results in efficacy, safety, and tolerability of the BP. This study compared the efficacy and tolerability of a macrogol-augmented BP (M-BP) with standard BP for routine colonoscopy in unselected patients. METHODS: Adults undergoing outpatient colonoscopy were randomized to either M-BP (one sachet of macrogol-based osmotic laxative (MBOL) twice daily for eight doses prior to standard preparation) or BP (split-dose of polyethylene glycol and sodium picosulfate). Bowel cleansing was assessed using the Ottawa BP scale. Risk factors for poor BP, patient satisfaction, and tolerance were recorded. RESULTS: This randomized trial was stopped due to futility after 14 months; at that point, 92 subjects were randomized to the study arm and 102 to the control arm. M-BP had a success rate of 71.7% (95% CI: 58.5-82.7%), while the BP had a success rate of 67.7% (95% CI: 54.9-78.8%), with a Pearson χ 2 test P-value of 0.639, which exceeded the cut-off for futility (0.313). In subgroup analyses, there were statistically significant decreases in the rates of successful BP in patients taking regular opioids and regular laxatives. Both preparations were well tolerated, with no difference between groups (BP - 5.3% and M-BP - 6.6% P = 0.66). CONCLUSION: The addition of MBOL prior to a standard BP in unselected subjects does not significantly improve bowel cleanliness at routine colonoscopy. The role of this laxative in patients at high risk of poor preparation warrants further investigation.

Postpolypectomy prophylactic clip closure for the prevention of delayed postpolypectomy bleeding: A systematic review.

Delayed postpolypectomy bleeding (DPPB) is the most common complication of colonoscopic polypectomy. Prophylactic clipping after an uncomplicated polypectomy is increasingly used, but it is unclear if this results in the prevention of DPPB. This study aimed to review prophylactic clip use and its effect on the rates of DPPB. MEDLINE, Embase, and the Cochran Library were systematically searched for studies (1995-March 2017) that used prophylactic hemoclips and assessed DPPB as an outcome. Of 1402 articles identified, nine papers were eligible for inclusion, evaluating 4311 patients and 7783 polyps; 118 patients experienced a DPPB, and 49 of these patients received prophylactic clips. There was no significant difference in DPPB rates in patients who received prophylactic clipping compared to those who did not (odd ratio: 0.8; 95% confidence interval: 0.36-1.77; P = 0.56). There was also no significant difference in the DPPB of polyps <20 mm compared with polyps ≥20 mm. Clip application for prophylactic management of an uncomplicated polypectomy has not been demonstrated to reduce the risk of DPPB, casting doubt on the use of this costly practice.

Multicenter randomised controlled trial comparing the high definition white light endoscopy and the bright narrow band imaging for colon polyps.

AIM: To compare high definition white light endoscopy and bright narrow band imaging for colon polyps' detection rates. METHODS: Patients were randomised to high definition white light endoscopy (HD-WLE) or the bright narrow band imaging (bNBI) during withdrawal of the colonoscope. Polyps identified in either mode were characterised using bNBI with dual focus (bNBI-DF) according to the Sano's classification. The primary outcome was to compare adenoma detection rates (ADRs) between the two arms. The secondary outcome was to assess the negative predictive value (NPV) in differentiating adenomas from hyperplastic polyps for diminutive rectosigmoid lesions. RESULTS: A total of 1006 patients were randomised to HD-WLE (n = 511) or bNBI (n = 495). The mean of adenoma per patient was 1.62 and 1.84, respectively. The ADRs in bNBI and HD-WLE group were 37.4% and 39.3%, respectively. When adjusted for withdrawal time (OR = 1.19, 95%CI: 1.15-1.24, P < 0.001), the use of bNBI was associated with a reduced ADR (OR = 0.69, 95%CI: 0.52-0.92). Nine hundred and thirty three polyps (86%) in both arms were predicted with high confidence. The sensitivity (Sn), specificity (Sp), positive predictive value and NPV in differentiating adenomatous from non-adenomatous polyps of all sizes were 95.9%, 87.2%, 94.0% and 91.1% respectively. The NPV in differentiating an adenoma from hyperplastic polyp using bNBI-DF for diminutive rectal polyps was 91.0%. CONCLUSION: ADRs did not differ between bNBI and HD-WLE, however HD-WLE had higher ADR after adjustment of withdrawal time. bNBI surpassed the PIVI threshold for diminutive polyps.

Outcomes and predictors of harmful relapse following liver transplantation for alcoholic liver disease in an Australian population.

BACKGROUND: Limited studies of patient survival and alcoholic relapse following transplantation for alcoholic liver disease have been described in Australian populations. AIM: To describe these outcomes in an Australian population, to determine the association between harmful alcoholic relapse and patient survival, and to examine pre-transplant variables associated with harmful relapse. METHODS: Single centre, retrospective review of consecutive patients transplanted at the South Australian Liver Transplant Unit. Relapse was identified by an independent investigator using case note review and confidential patient questionnaire. RESULTS: A total of 87 patients (median age 52 years, 84% male, median Model for End-Stage Liver Disease (MELD) score 18) was included in the study with a median follow-up time of 50 months. The 1-, 3- and 5-year survival of patients was 93.1, 87.4 and 82.0% respectively. Two deaths were directly attributable to graft failure due to alcohol. Fourteen (16%) patients fulfilled criteria for harmful relapse and 18 (21%) patients experienced any form of relapse to alcohol. Harmful relapse was associated with increased mortality (hazard ratio (HR) 3.2, 95% confidence interval (CI) 1.1-9.7, P = 0.041). Only two factors were independently associated with harmful relapse on multivariate analysis; prior alcohol rehabilitation (HR 8.4, 95% CI 2.5-28.4, P = 0.001) and single versus married status (HR 0.09, 95% CI 0.02-1.2, P = 0.019). CONCLUSION: Good patient survival outcomes were seen for this South Australian population. Harmful alcohol relapse occurs in a minority of patients and rarely results in direct graft loss. Modifiable pre-transplant factors that predict harmful relapse were not identified.

White Diet with split-dose Picosalax is preferred, better tolerated, and non-inferior to day-before clear fluids with polyethylene glycol plus sodium picosulfate-magnesium citrate for morning colonoscopy: A randomized, non-inferiority trial.

BACKGROUND AND AIM: Bowel preparations with polyethylene glycol (PEG) and clear fluids are often poorly tolerated. We compared an innovative low-residue White Diet and low-volume, split-dose Picosalax with the standard preparation at our institution of day-before clear fluids and combination PEG plus sodium picosulfate/magnesium citrate (SPMC). METHODS: Adults undergoing morning colonoscopy were randomized to either the White Diet and split-dose, two sachets of Picosalax (WD/PICO) or day-before clear fluids and 1-L PEG plus two sachets of SPMC (CF/PEG + SPMC). The primary endpoint was successful bowel preparation defined by an Ottawa bowel preparation score ≤ 6. An intention-to-treat analysis with a predefined non-inferiority margin of 15% was used to compare efficacy. RESULTS: A total of 250 patients were randomized (125 WD/PICO and 125 CF/PEG + SPMC). WD/PICO was non-inferior to CF/PEG + SPMC for successful bowel preparation by intention-to-treat analysis (58% WD/PICO vs 62% CF/PEG + SPMC, 95%CI: -14.2 to 6.2%) and per-protocol analysis (64% WD/PICO vs 65% CF/PEG + SPMC, 95%CI: -11.3 to 9.4%). Patients in the WD/PICO group reported greater satisfaction with the diet (P < 0.001), greater ease of following the diet (P < 0.001), and improved experience compared with prior colonoscopy (P < 0.0001), less bloating (P = 0.02), less weakness (P = 0.046), less hunger (P < 0.0001), and less interference with daily activities (P = 0.001). Procedure/withdrawal times and adenoma detection rates were similar between groups. CONCLUSION: Bowel preparation with the White Diet and low-volume, split-dose Picosalax was preferred and better tolerated without detriment to bowel preparation success compared with clear fluids and combination PEG plus SPMC for morning colonoscopy.

A Blood Test for Methylated BCAT1 and IKZF1 vs. a Fecal Immunochemical Test for Detection of Colorectal Neoplasia.

OBJECTIVES: To compare the performance of a new blood test for colorectal cancer (CRC) to an established fecal immunochemical test (FIT) in a study population with the full range of neoplastic and non-neoplastic pathologies encountered in the colon and rectum. METHODS: Volunteers were asked to complete a FIT prior to colonoscopy. Blood was collected after bowel preparation but prior to colonoscopy, and plasma was assayed for the presence of methylated BCAT1 and IKZF1 DNA using a multiplex real-time PCR assay. Sensitivity and specificity estimates for the blood test were calculated from true- and false-positive rates for neoplasia and compared with FIT at a range of fecal hemoglobin (Hb) concentration positivity thresholds. RESULTS: In total, 1,381 volunteers (median age 64 years; 49% male) completed both tests prior to colonoscopy. Estimated sensitivity of the BCAT1/IKZF1 blood test for CRC was 62% (41/66; 95% confidence interval 49-74%) with a specificity of 92% (1207/1315; 90-93%). FIT returned the same specificity at a cutoff of 60 µg Hb/g, at which its corresponding sensitivity for cancer was 64% (42/66; 51-75%). In the range of commonly used FIT cutoffs, respective cancer sensitivity and specificity estimates with FIT were: 59% (46-71%) and 93% (92-95%) at 80 µg Hb/g, and 79% (67-88%) and 81% (78-83%) at 10 µg Hb/g. Although estimated sensitivities were not significantly different between the two tests for any stage of cancer, FIT showed a significantly higher sensitivity for advanced adenoma at the lower cutoffs. Specificity of FIT, but not of the BCAT1/IKZF1 blood test, deteriorated substantially in people with overt blood in the feces. When combining FIT (cutoff 10 µg Hb/g) with the BCAT1/IKZF1 blood test, sensitivity for cancer was 89% (79-96%) at 74% (72-77%) specificity. CONCLUSIONS: A test based on detection of methylated BCAT1/IKZF1 DNA in blood has comparable sensitivity but better specificity for CRC than FIT at the commonly used positivity threshold of 10 µg Hb/g. Further evaluation of the new test relative to FIT in the population screening context is now required to fully understand the potential advantages and disadvantages of these biomarkers in screening.

Evaluation of an assay for methylated BCAT1 and IKZF1 in plasma for detection of colorectal neoplasia.

BACKGROUND: Specific genes, such as BCAT1 and IKZF1, are methylated with high frequency in colorectal cancer (CRC) tissue compared to normal colon tissue specimens. Such DNA may leak into blood and be present as cell-free circulating DNA. We have evaluated the accuracy of a novel blood test for these two markers across the spectrum of benign and neoplastic conditions encountered in the colon and rectum. METHODS: Circulating DNA was extracted from plasma obtained from volunteers scheduled for colonoscopy for any reason, or for colonic surgery, at Australian and Dutch hospitals. The extracted DNA was bisulphite converted and analysed by methylation specific real-time quantitative PCR (qPCR). A specimen was deemed positive if one or more qPCR replicates were positive for either methylated BCAT1 or IKZF1 DNA. Sensitivity and specificity for CRC were estimated as the primary outcome measures. RESULTS: Plasma samples were collected from 2105 enrolled volunteers (mean age 62 years, 54 % male), including 26 additional samples taken after surgical removal of cancers. The two-marker blood test was run successfully on 2127 samples. The test identified 85 of 129 CRC cases (sensitivity of 66 %, 95 % CI: 57-74). For CRC stages I-IV, respective positivity rates were 38 % (95 % CI: 21-58), 69 % (95 % CI: 53-82), 73 % (95 % CI: 56-85) and 94 % (95 % CI: 70-100). A positive trend was observed between positivity rate and degree of invasiveness. The colonic location of cancer did not influence assay positivity rates. Gender, age, smoking and family history were not significant predictors of marker positivity. Twelve methylation-positive cancer cases with paired pre- and post-surgery plasma showed reduction in methylation signal after surgery, with complete disappearance of signal in 10 subjects. Sensitivity for advanced adenoma (n = 338) was 6 % (95 % CI: 4-9). Specificity was 94 % (95 % CI: 92-95) in all 838 non-neoplastic pathology cases and 95 % (95 % CI: 92-97) in those with no colonic pathology detected (n = 450). CONCLUSIONS: The sensitivity for cancer of this two-marker blood test justifies prospective evaluation in a true screening population relative to a proven screening test. Given the high rate of marker disappearance after cancer resection, this blood test might also be useful to monitor tumour recurrence. TRIAL REGISTRATION: ACTRN12611000318987 .

Screening colonoscopy in Australia.

Colorectal cancer (CRC) is a global epidemic predominantly affecting Western countries. It is the second leading cause of cancer-related deaths in Australia with one in 12 Australians affected by this condition by the age of 85 years. Appropriate preventive measures by screening followed by colonoscopy can detect cancer and precancerous lesions, which are potentially curable. The National Bowel Cancer Screening Program (NBCSP) is a national screening program implemented by the Australian Government aimed at reducing morbidity and mortality from bowel cancer by actively recruiting and screening the target population. The long-term goal of the program is to include the at-risk population (50-74 years of age) in a biennial screening program. Newer technologies could have a potential role in screening programs by enhancing adenoma detection rates. However, until more evidence is available, improving screening uptake and bowel preparation strategies are the prime focus in reducing CRC-related morbidity and mortality.