Nicholas Tutticci

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.

Sessile serrated adenomas/polyps with cytologic dysplasia: a triple threat for interval cancer

Sessile serrated adenomas/polyps (SSA/P) are strongly associated with interval cancer. Interval cancers require a precursor lesion that is either rapidly progressive, evades detection, or foils attempts at resection. SSA/Ps with cytologic dysplasia (SSA/P-Ds) fulfill all 3 of these criteria. SSA/P-D is endoscopically identifiable because the dysplasia is often associated with a change in surface morphology or a nodule. The dysplasia can mimic that of conventional adenoma. SSA/P-D may be at high risk of incomplete resection because of this mimicry because the endoscopist may resect only the dysplastic component resembling conventional adenoma, leaving the unrecognized surrounding nondysplastic component. Pathologists may likewise fail to recognize SSA/P-D if they disregard or overlook serrated histology in what appears to be a conventional adenoma or if they receive only the dysplastic nodule in an incompletely resected specimen. It is crucial that both the endoscopist and the pathologist are aware of the concept of SSA/P-D, which may improve recognition of these lesions. Close collaboration is important, and when a potential SSA/P-D is submitted for histologic examination, this possibility should be made clear in the pathology request to ensure complete reporting. The significance of serrated lesions has escalated in recent years because their importance as colorectal cancer (CRC) precursors has been recognized. Approximately 20% to 30% of all CRC is thought to develop along the serrated neoplasia pathway, and it is hypothesized that the relative failure of colonoscopy to protect against CRC in the proximal colon is related to the poor detection or subtotal resection of serrated lesions. These precursors, most notably sessile serrated adenomas/polyps (SSA/Ps), are strongly associated with CRC identified in the surveillance period after complete colonoscopy, termed interval cancer. Cancers detected within this interval require a precursor lesion that is either rapidly progressive, evades detection, or foils attempts at resection. SSA/Ps with cytologic dysplasia (SSA/P-Ds) fulfill all 3 of these criteria and represent a critically underrecognized link in the incomplete effectiveness of colonoscopic CRC prevention. We propose that SSA/P-D is often endoscopically identifiable, and poor recognition and incomplete resection is a result of the lesions’ peculiar features of both imperceptibility and mimicry. Refocused attention on awareness, recognition, and resection may help in addressing interval cancer rates. SSA/Ps typically have little or no cytologic dysplasia; however, it is clear that molecular changes can result in dysplasia (SSA/P-D). This dysplasia may be indistinguishable from the “conventional” dysplasia seen in adenomas. SSA/Ps commonly have activating mutations of the BRAF gene (proto-oncogene B-Raf) and often develop excessive methylation of the CpG promoter regions of mismatch repair genes (CpG island methylator phenotype [CIMP]). Although there are several putative mechanisms for neoplastic progression in serrated lesions, the most wellrecognized pathway to CRC involves hypermethylation of mismatch repair genes such as MLH-1 (MutL homolog 1), resulting in microsatellite instability (MSI) (Fig. 1.) SSA/PDs resembling conventional adenomas frequently exhibit MLH-1 hypermethylation and MSI in their dysplastic foci and are thought to represent a transition form to BRAFmutated, CIMP-high (CIMP-H), MSI CRC comprising 9% to 12% of CRCs. The progression rate of SSA/P-D to CRC is unknown but is thought to be rapid because equivalent

Characterization and significance of protrusions in the mucosal defect after cold snare polypectomy.

BACKGROUND Cold snare polypectomy (CSP) is widely practiced; however, the endoscopic features of the CSP mucosal defect have not been studied. In particular, protrusions within the cold snare defect (CSDPs) may create concern for residual polyp. The frequency and constituents of this phenomenon are unknown. OBJECTIVE To describe the frequency, predictors, and histologic constituents of CSDPs. DESIGN Prospective observational study. SETTING Tertiary-care hospital endoscopy unit. PATIENTS Eighty-eight consecutive patients undergoing CSP for a polyp ≤ 10 mm in size. INTERVENTION Inspection of the cold snare mucosal defect with high-definition white light and biopsy sampling of CSDPs for separate histologic assessment, when present. MAIN OUTCOME MEASUREMENT Frequency and constituents of CSDPs. RESULTS Two hundred fifty-seven consecutive polyps ≤ 10 mm in size were removed in 88 patients (50 men [57%], mean age 63 years). Polyps were predominately adenomatous (162, 63%), located in the proximal colon (159, 62%) and flat (200, 78%). Mean lesion size was 5.5 mm (range, 2-10 mm). High-grade dysplasia was present in a single polyp for which the defect was bland. CSDPs occurred in 36 polypectomies (14%). CSDPs were associated with polyp size ≥ 6 mm (odds ratio, 3.7; P < .001 multivariable analysis) but not age, sex, lesion, histopathology, morphology, or location. Histopathologic examination of CSDPs revealed submucosa in 34 (94%) and muscularis mucosa in 29 (80%). No residual adenomatous or serrated polyp tissue was detected. LIMITATIONS Single-center study. Small number of polyps with high-grade dysplasia. CONCLUSION Protrusions are common within the CSP mucosal defect and are associated with polyp size ≥ 6 mm. CSDPs do not represent vascular structures, do not contain residual polyp, and are not associated with adverse outcomes in short-term follow-up. However, CSDPs represent incomplete mucosal layer resection.

Caught in the act: endoscopic characterization of sessile serrated adenomas with dysplasia

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Endoscopic mucosal resection of laterally spreading lesions involving the ileocecal valve: technique, risk factors for failure, and outcomes

BACKGROUND AND STUDY AIMS Endoscopic mucosal resection (EMR) of laterally spreading lesions (LSLs) involving the ileocecal valve (ICV) is technically demanding. Conventionally, these lesions are considered too challenging for endoscopic therapy and are primarily managed surgically. The aims of the study were to describe effectiveness, safety, and outcomes following EMR of LSLs at the ICV. PATIENTS AND METHODS This was a single-center, prospective, observational, cohort study performed at an academic, tertiary referral center. Patients undergoing EMR for LSLs ≥ 20 mm involving the ICV were recruited over a 5-year period. Standard or cap-assisted colonoscopy with inject-and-resect EMR technique was performed with standardized post-EMR management. Procedural success, safety, and outcomes compared with non-ICV LSLs managed during the same period were analyzed. RESULTS A total of 53 patients with ICV LSLs were referred for EMR (median age 69 years; median lesion size 35.0 mm; 52.8 % females). Six patients went directly to surgery because of an endoscopic diagnosis of malignancy (n = 2) or technical failure of EMR (n = 4). EMR achieved complete adenoma clearance in 44 out of 47 attempted (93.6 %). Surgery was ultimately avoided in 43/53 (81.1 %). Complications included bleeding in 6.4 %. There were no perforations or strictures. Early adenoma recurrence was detected in 7/40 patients (17.5 %), and 1/22 (4.5 %) had late recurrence. All were successfully managed endoscopically. Factors associated with failure of ICV EMR were ileal infiltration and involvement of both ICV lips. CONCLUSIONS In the majority of cases, LSL involving the ICV can be effectively treated by EMR on an outpatient basis. In specialized centers, complications are infrequent, and  > 80 % of patients ultimately avoid surgery. Trial registered at ClinicalTrials.gov (NCT01368289).

Advanced endoscopic resection in the colon: recent innovations, current limitations and future directions

The major health burden of colorectal cancer is reduced by colonoscopic polypectomy. The majority of polyps encountered are diminutive in size and easily removed; however, endoscopic removal of lesions >20 mm in size is also effective and safe. Techniques have progressed, advancing the boundaries of endoscopic therapy to include resection of circumferential lesions and selected submucosal invasive cancers. While there are cost and safety advantages over surgical management, specific limitations of endoscopic resection remain, chiefly bleeding, perforation and recurrence. Recent studies highlight the utility of risk stratification and demonstrate the effectiveness of endoscopic treatment of complications; however, strategies for prevention remain elusive. Prediction of submucosal invasive cancers through systematic assessment of lesion morphology and surface pattern is now established. Harnessing submucosal invasive cancer prediction and risk stratification allows a shift toward lesion-specific therapy, the next paradigm in the management of advanced colonic lesions.

Endoscopic resection of advanced and lateral spreading papillary tumours

Historically, neoplasia of the duodenal papilla has been managed surgically, which may be associated with substantial morbidity and mortality. In the absence of invasive cancer, even lesions with extensive lateral duodenal wall involvement, or limited intraductal extension may be cured endoscopically with a superior safety profile. Endoscopic papillectomy is associated with greater risks of adverse events such as bleeding than resection elsewhere in the gastrointestinal tract. Additionally site‐specific complications such as pancreatitis exist. A structured approach to lesion assessment, adherence to technical aspects of resection, endoscopic management of complications and post‐resection surveillance is required. Advances have been made in all facets of endoscopic papillary resection since its introduction in the 1980s; extending the boundaries of endoscopic cure, optimizing outcomes and enhancing patient safety. These will be the focus of the present review.

Endoscopic resection of advanced and laterally spreading duodenal papillary tumors.

Historically, neoplasia of the duodenal papilla has been managed surgically, which may be associated with substantial morbidity and mortality. In the absence of invasive cancer, even lesions with extensive lateral duodenal wall involvement, or limited intraductal extension may be cured endoscopically with a superior safety profile. Endoscopic papillectomy is associated with greater risks of adverse events such as bleeding than resection elsewhere in the gastrointestinal tract. Additionally site‐specific complications such as pancreatitis exist. A structured approach to lesion assessment, adherence to technical aspects of resection, endoscopic management of complications and post‐resection surveillance is required. Advances have been made in all facets of endoscopic papillary resection since its introduction in the 1980s; extending the boundaries of endoscopic cure, optimizing outcomes and enhancing patient safety. These will be the focus of the present review.

Endoscopic resection of subtotal or completely circumferential laterally spreading colonic adenomas: technique, caveats, and outcomes.

BACKGROUND AND STUDY AIMS Endoscopic mucosal resection (EMR) is an established treatment for large (≥ 20 mm) laterally spreading lesions (LSLs). LSLs with complete or subtotal (> 90 %) circumferential extent (C-LSLs) are generally referred for surgery. Data on technique, efficacy, and safety of EMR for these lesions are absent. The aim of this study was to describe the technique and long-term outcomes of EMR for C-LSLs. PATIENTS AND METHODS Prospective observational study of consecutive patients referred for EMR of LSL at a tertiary care center over 63 months to April 2015. Amongst 979 patients with LSL, 12 patients with C-LSL were seen. RESULTS All lesions were tubulovillous adenomas with granular 0 - IIa + Is morphology. Median longitudinal extent was 95 mm (range 60 - 160), 58 % were located in the rectum, and 3 lesions (25 %) had complete circumferential involvement. EMR technical success was 100 %. There were no major adverse events. Symptomatic stricturing occurred in 2 cases (17 %) and was treated with endoscopic balloon dilation (median 4 sessions). Median follow up is 13 months. Minor residual adenoma was found in 7 (58 %) at first surveillance colonoscopy and was treated with snare excision. A total of 10 patients have completed a second surveillance colonoscopy with minor residual adenoma found in only 1 case. No patient required surgery or developed cancer in long-term follow-up. CONCLUSIONS Endoscopic resection of C-LSL is feasible and safe. Minor residual adenoma is common but endoscopically treatable with long-term cure. Symptomatic stricturing amenable to balloon dilation may occur. Empiric surgical referral for C-LSL based on extensive circumferential involvement may be avoided.ClinicalTrials.gov NCT01368289.

Expanding the Boundaries of Endoscopic Resection: Circumferential Laterally Spreading Lesions of the Duodenum

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