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.

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.

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.

Prophylactic endoscopic coagulation to prevent bleeding after wide-field endoscopic mucosal resection of large sessile colon polyps.

BACKGROUND & AIMS: Clinically significant postendoscopic mucosal resection bleeding (CSPEB) is the most frequent significant complication of wide-field endoscopic mucosal resection (WF-EMR) of advanced mucosal neoplasia (sessile or laterally spreading colorectal lesions > 20 mm). CSPEB requires resource-intensive management and there is no strategy for preventing it. We investigated whether prophylactic endoscopic coagulation (PEC) reduces the incidence of CSPEB. METHODS: We performed a prospective randomized controlled trial of 347 patients (mean age, 67.1 y; 55.3% with proximal colonic lesions) undergoing WF-EMR for advanced mucosal neoplasia at 3 Australian tertiary referral centers. Patients were assigned randomly (1:1) to groups receiving PEC (n = 172) or no additional therapy (n = 175, controls). PEC was performed with coagulating forceps, applying low-power coagulation to nonbleeding vessels in the resection defect. CSPEB was defined as bleeding requiring admission to the hospital. The primary end point was the proportion of CSPEB. RESULTS: Patients in each group were similar at baseline. CSPEB occurred in 9 patients receiving PEC (5.2%) and 14 controls (8.0%; P = .30). CSPEB was associated significantly with proximal colonic location on multivariate analysis (odds ratio, 3.08; P = .03). Compared with the proximal colon, there was a significantly greater number (3.8 vs 2.1; P = .002) and mean size (0.5-1 vs 0.3-0.5 mm; P = .04) of visible vessels in the distal colon. CONCLUSIONS: PEC does not significantly decrease the incidence of CSPEB after WF-EMR. There were significantly more and larger vessels in the WF-EMR mucosal defect of distal colonic lesions, yet CSPEB was more frequent with proximal colonic lesions. ClinicalTrials.gov NCT01368731.

Hot avulsion: a modification of an existing technique for management of nonlifting areas of a polyp (with video).

BACKGROUND: Endoscopic management of the nonlifting areas of a colonic polyp is a significant challenge. The traditional approach has been to use ablative techniques with mixed long-term results. OBJECTIVE: To evaluate the safety and efficacy of hot avulsion (HA), a modification in the use of hot biopsy forceps in the management of the nonlifting areas of a colonic polyp. DESIGN: Retrospective review of data from a prospectively maintained colonic Endoscopic Mucosal Resection database. SETTING: Tertiary referral hospital. PATIENTS AND INTERVENTION: Twenty patients in whom HA was used as part of the polypectomy technique. MAIN OUTCOME MEASUREMENTS: Location and size of polyp, reasons for nonlifting, immediate success, residual rates, and adverse events. RESULTS: In our 20 patients studied, the main reasons for nonlifting were scarring from previous EMR attempts in 55% and scarring from previous biopsy in 35%. Mean size of avulsion was 4.4 mm (range, 1-15 mm). At the index procedure, HA was successful in removing macroscopic adenomatous tissue in all patients. At follow-up examinations, 85% (17/20) had no macroscopic or microscopic neoplasia residual and 15% (3/20) had a small area of residual that was easily treated with repeat HA. There were no immediate or long-term adverse events. LIMITATIONS: Nonrandomized, single-center experience. CONCLUSIONS: HA appears to be a safe and effective adjunct treatment to snare polypectomy for nonlifting areas of a colonic polyp. Further randomized multicenter studies are required with direct comparison to established techniques.

Wire assisted transpancreatic septotomy, needle knife precut or both for difficult biliary access.

BACKGROUND AND AIMS: Pre-cut techniques, the most commonly described being needle knife papillotomy (NK), have been used to facilitate biliary access in failed standard biliary cannulation (BC). Transpancreatic septotomy (TS) is a pre-cut technique with limited outcome data. We aim to assess the outcomes of wire assisted transpancreatic septotomy (WTS) as the primary pre-cut technique after initial failed attempted BC and to compare these with outcomes of primary NK. METHODS: We retrospectively reviewed all endoscopic retrograde cholangiopancreatographies (ERCPs) performed by endoscopists who performed WTS over a 3-year period. We selected cases where WTS and/or NK were performed, and these cases were reviewed to assess for procedure related complications and BC success. RESULTS: During the study period 1336 ERCPs were performed. WTS was performed in 53 cases. In seven cases WTS and NK were performed sequentially (resulting in immediate cannulation in all these cases). Immediate BC was achieved on first attempt in 36 (68%) WTS cases and in a further 14 cases on a repeat attempt (cumulative BC rate 94%). During the same period 66 (5%) patients underwent primary NK. In these cases initial cannulation was achieved in 50 (76%) cases and cannulation on repeat attempt in six cases (cumulative success rate 85%). Complications occurred in three WTS patients (5.6%) and seven NK patients (10.6%). The differences were not statistically significant. CONCLUSIONS: Wire assisted transpancreatic septotomy is a safe and effective alternative technique to traditional NK in patients who have failed standard BC techniques. It also allows other pre-cut techniques such as NK to be used should initial WTS be unsuccessful.

Endoscopic skills training in a simulated clinical setting.

BACKGROUND/AIM: We describe a simulation and scenario-based model of training in gastrointestinal endoscopic hemostasis, which combines acquisition of procedural and problem-solving skills in a close to reality simulated clinical setting. METHODS: Two day courses in endoscopic hemostasis were conducted at the Clinical Training and Education Centre, the University of Western Australia, Perth, Australia. In total, 23 trainees were enrolled. The Erlangen Endo-Trainer simulator, porcine specimens of esophagus, stomach, and duodenum with a range of simulated bleeding sources, a separate catheter and a pump to simulate massive bleeding, and a full arm model with injectable veins were used. The SimMan monitor and software package were used to simulate hemodynamic parameters and electrocardiogram. Faculty members adjusted the rate of bleeding and vital parameters. The exercise was video recorded. On the first day, the group underwent simulator training in techniques of endoscopic hemostasis. On the second day, participants were scenario-based trained in full management of a "bleeding patient," which included resuscitation, sedation, endoscopy, and hemostasis, acting as leaders in teams of three. The course was evaluated by participants using a standardized questionnaire. RESULTS: A complex clinical setting of acute gastrointestinal bleeding was recreated with a high degree of realism. All participants reported that the simulated clinical scenario was a positive learning experience, helpful in managing complications and performing complex problem-solving tasks in a dynamic environment. CONCLUSIONS: Scenario and simulation-based training in endoscopic hemostasis may provide an opportunity to improve procedural skills and acquire practical experience in managing this medical emergency, which requires the ability to process, integrate, and adequately and quickly respond to complex information in unexpected conditions working as a team leader.

Outcomes of endoscopic resection of large colorectal neoplasms: an Australian experience.

BACKGROUND AND AIMS: Endoscopic resection of large colorectal neoplasms is increasingly being used as an alternative to surgery. However data on failure rates, safety and long-term outcomes remain limited. The aim of the study was to report short- and long-term outcomes from endoscopic resection of large colorectal neoplasms from a single centre and use a model to predict mortality had surgery been performed. METHODS: Consecutive patients referred for endoscopic resection of large (> or = 20 mm) colorectal neoplasms from January 2001 to February 2008 were included. Resection details were recorded in a prospectively maintained database. Data was collected on 30-day complication rates, and follow-up colonoscopy findings. The Colorectal-POSSUM score was used to estimate mortality from open surgery. RESULTS: There were 154 large neoplasms in 140 patients. Mean age was 68 years (range 22-94). Mean neoplasm size was 26 mm (range 20-80 mm, 24 > or = 40 mm). Complete endoscopic removal was achieved in 95% of cases. Twenty patients were referred for surgery (14%). In the endoscopy group, there were no deaths within 30 days. Twelve patients had a complication including two perforations. Endoscopic follow-up data was available in 90% of cases and five patients (4%) were found to have residual adenoma that was treated endoscopically with subsequent clearance. If surgery had been performed, the mean predicted mortality was 2.2% (range 0.5-10%). There were two deaths (10%) in patients who underwent elective surgery within 30 days. CONCLUSION: Endoscopic resection of large colorectal neoplasms is safe and effective even for very large benign neoplasms. When the lesion is endoscopically resectable this should be the preferred treatment.

Routine colonic mucosal biopsy and ileoscopy increases diagnostic yield in patients undergoing colonoscopy for diarrhea.

BACKGROUND AND AIMS: In patients undergoing colonoscopy for diarrhea, when the examination is normal, the role of routine mucosal biopsy remains controversial, particularly in the open-access setting. It is uncertain whether routine ileoscopy adds anything to colonoscopy alone. We aimed to assess the yield of mucosal biopsy and ileoscopy in patients with diarrhea. METHODS: We retrospectively reviewed all colonoscopies performed for diarrhea over a 9-year period in a tertiary referral center with an open-access service. We then selected cases where the examination was normal and biopsies were performed. The histopathology reports of these selected cases were then reviewed. RESULTS: There were 1131 cases identified. The mucosal examination was normal in 465 cases (41%); 362 of these had colonic biopsies performed. Histology was normal in 316 cases (87%) and was non-specific in 28 cases (8%). Significant histopathology was present in 18 cases (5%) with a significantly higher prevalence of microscopic colitis in patients above 60 years old. Ileoscopy was performed in 508 cases and was abnormal in 26 cases (5%). The abnormality on ileoscopy was the sole abnormality in 13 cases (3%). CONCLUSIONS: Routine colonic mucosal biopsy and ileoscopy each identify significant additional pathology in 5% of cases when investigating patients with diarrhea, and are recommended as routine practice in this setting. We found ileal biopsy unhelpful when ileoscopy was normal.