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.

The modern management of Barrett's oesophagus and related neoplasia: role of pathology.

Modern management of Barrett's oesophagus and related neoplasia essentially focuses upon surveillance to detect early low-risk neoplastic lesions and offering organ-preserving advanced endoscopic therapies, while traditional surgical treatments of oesophagectomy and lymph node clearance with or without chemoradiation are preserved only for high-risk and advanced carcinomas. With this evolution towards figless invasive therapy, the choice of therapy hinges upon the pathological assessment for risk stratifying patients into those with low risk for nodal metastasis who can continue with less invasive endoscopic therapies and others with high risk for nodal metastasis for which surgery or other forms of treatment are indicated. Detection and confirmation of neoplasia in the first instance depends upon endoscopic and pathological assessment. Endoscopic examination and biopsy sampling should be performed according to the recommended protocols, and endoscopic biopsy interpretation should be performed applying standard criteria using appropriate ancillary studies by histopathologists experienced in the pathology of Barrett's disease. Endoscopic resections (ERs) are both diagnostic and curative and should be performed by clinicians who are skilled with advanced endoscopic techniques. Proper preparation and handling of ERs are essential to assess histological parameters that dictate the curative nature of the procedure. Those parameters are adequacy of resection and risk of lymph node metastasis. The risk of lymph node metastasis is determined by depth invasion and presence of poor differentiation and lymphovascular invasion. Those adenocarcinomas with invasion up to muscularis mucosae (pT1a) and those with superficial submucosal invasion (pT1b) up to 500 µ with no poor differentiation and lymphovascular invasion and negative margins may be considered cured by endoscopic resections.

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.

Early Barrett esophagus-related neoplasia in segments 1 cm or longer is always associated with intestinal metaplasia.

The assumption that intestinal metaplasia is a prerequisite for intraepithelial neoplasia/dysplasia and adenocarcinoma in the distal esophagus has been challenged by observations of adenocarcinoma without associated intestinal metaplasia. This study describes our experience of intestinal metaplasia in association with early Barrett neoplasia in distal esophagus and gastroesophageal junction. We reviewed the first endoscopic mucosal resection of 139 patients with biopsy-proven neoplasia. In index endoscopic mucosal resection, 110/139 (79%) cases showed intestinal metaplasia. Seven had intestinal metaplasia on prior biopsy specimens and three had intestinal metaplasia in subsequent specimens, totaling 120/139 (86%) patients showing intestinal metaplasia at some point supporting the theory of sampling error for absence of intestinal metaplasia in some cases. Those without intestinal metaplasia (13%) were enriched for higher stage disease (T1a Stolte m2 or above) supporting the assertion of obliteration of intestinal metaplasia by the advancing carcinoma. All cases of intraepithelial neoplasia and T1a Stolte m1 carcinomas had intestinal metaplasia (42/42). The average density of columnar-lined mucosa showing goblet cells was significantly less in shorter segments compared to those ≥3 cm (0.31 vs 0.51, P=0.0304). Cases where segments measured less than 1 cm were seen in a higher proportion of females and also tended to lack intestinal metaplasia. We conclude that early Barrett neoplasia is always associated with intestinal metaplasia; absence of intestinal metaplasia is attributable to sampling error or obliteration of residual intestinal metaplasia by neoplasia and those with segments less than 1 cm show atypical features for Barrett-related disease (absent intestinal metaplasia and female gender), supporting that gastroesophageal junction adenocarcinomas are heterogeneous.

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.

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.

Image analysis of liver collagen using sirius red is more accurate and correlates better with serum fibrosis markers than trichrome.

BACKGROUND: Collagen proportional area (CPA) determined by quantitative digital image analysis better quantifies liver fibrosis than histological stage; however, its clinical use has been limited by non-standardized methods. AIM: This study aimed to compare CPA obtained using different staining methods, magnifications and biopsy sizes. METHODS: Two hundred and forty-nine patients with chronic hepatitis C who had a liver biopsy and serum fibrosis markers performed were included. CPA was measured either using a sirius red (CPAs) or a trichrome (CPAt) stain. RESULTS: CPAs measured at 20× and 40× magnifications generated similar outcomes with interclass correlation (ICC) coefficient of 0.98. Compared with trichrome, sirius red staining had much less variation with an ICC coefficient of 0.99 for slides stained in the same batch and 0.92 in different batches. Mean CPAs was higher than mean CPAt by 3.53%, P < 0.001. Morphological analysis found that sirius red detected delicate fibrous septa and spurs better than trichrome. Both CPAs and CPAt correlated well with Metavir stage, whereas CPAs had better ability to detect cirrhosis with the area under ROC curve of 0.95. Overall CPA had superior correlation with serum markers of fibrosis in Metavir F2-F4 than that in F0-F1 and CPAs correlated better with serum fibrosis markers than CPAt in Metavir F0-F1. Multivairate analysis found that HA, α2-macroglobulin, platelet count and albumin were independently correlated with CPAs and only HA was independently correlated with CPAt. CONCLUSIONS: Sirius red staining for CPA determination was more accurate and reliable for quantifying hepatic collagen compared with trichrome staining.

Gastric intraepithelial neoplasia in a Western population.

BACKGROUND AND STUDY AIMS: Descriptions of the natural history and endoscopic appearances of gastric dysplasia/intraepithelial neoplasia (IEN) that originate mainly from Europe. Currently, there are no Australian data available. We aimed to document endoscopic appearances and progression rates of gastric IEN and to determine the significance of indefinite for IEN. PATIENTS AND METHODS: This is a retrospective study, in which cases diagnosed with gastric IEN were identified between 2000 and 2009. Endoscopic appearances, progression rates to more advanced IEN or cancer, and long-term outcomes were recorded. RESULTS: A total of 160 cases with IEN (26.9% high grade, 57.5% low grade, 15.6% indefinite) were identified. The mean age was 67.8 years and 53.8% were men. Endoscopic lesions were polypoid in 29.4% and nonpolypoid in 70.6%. The most common location was the antrum (58.7%). Forty patients had an intervention and 76 underwent endoscopic follow-up only. Twenty-two cancers were diagnosed; three who had an intervention were diagnosed within 12 months, one with low-grade intraepithelial neoplasia developing a cancer after 9.9 years, and 13 undergoing surveillance only, were diagnosed with cancer within 12 months of index endoscopy. Five cases had cancer after a mean of 2.6 years. Forty-seven cases initially labelled as indefinite; following rereview 25 remained unchanged, 11 reclassified as negative for IEN, 10 as low grade, and one as high grade. Three of these cases developed cancer over the study period. CONCLUSION: We concluded that (a) majority of gastric IEN are associated with endoscopic lesions, (b) high rate of early cancer diagnosis was observed (c) rates of progression to cancer were lower than reported rates, and (d) indefinite for IEN is not innocuous requiring an expert pathologist's review.

A cohort study of missed and new cancers after esophagogastroduodenoscopy.

OBJECTIVES: Little is known about missed rates of upper gastrointestinal cancer (UGC) in Western populations, with most data originating from Japanese centers quoting high missed rates of 23.5-25.8%. The objective of this study was to better define missed rates of esophagogastroduodenoscopy (EGD) and the natural history of UGC in a Western population that underwent an initial EGD without cancer, but were subsequently diagnosed with a UGC. Our hypothesis was that a normal EGD rarely misses the detection of UGC. METHODS: This is a retrospective cohort study. A prospectively maintained electronic database was used to identify all patients who underwent EGD between 1990 and 2004 at the study institution. Patients in this cohort who were diagnosed with UGC before 2006 were identified through the Western Australian Cancer Registry. We defined missed cancers as those diagnosed within 1 year of EGD, possible missed cancers as those diagnosed 1-3 years after EGD, and new cancers as those diagnosed more than 3 years after EGD. This study had no interventions and was conducted at a tertiary referral center. The main outcome measurement included UGC. RESULTS: Of the 28,064 EGDs performed, UGC was diagnosed subsequent to the procedure in 116 cases (0.41%). There were 29 missed cancers, 26 possible missed cancers, and 75 new cancers. Of the missed cancers, 11 were esophageal, 15 were gastric, and 3 were duodenal. In 69% (n=20) of the missed cancers, an abnormality was described at the site of malignancy. In 59% (n=17) of the missed cancers, the indication for EGD was an alarm symptom of dysphagia or suspected blood loss. In an univariate analysis, the presence of an alarm symptom was related to missed cancers, whereas operator experience, trainee participation, and usage of newer equipment were not. One of the main limitations of this study is that it was a retrospective review. CONCLUSIONS: UGC is rare after normal EGD, confirming the high accuracy of EGD. Institutional approval was granted for the conduct of this study.