Spiro C. Raftopoulos

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.

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.

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.

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.

Australian clinical practice guidelines for the diagnosis and management of Barrett's esophagus and early esophageal adenocarcinoma

Barretts esophagus (BE), a common condition, is the only known precursor to esophageal adenocarcinoma (EAC). There is uncertainty about the best way to manage BE as most people with BE never develop EAC and most patients diagnosed with EAC have no preceding diagnosis of BE. Moreover, there have been recent advances in knowledge and practice about the management of BE and early EAC. To aid clinical decision making in this rapidly moving field, Cancer Council Australia convened an expert working party to identify pertinent clinical questions. The questions covered a wide range of topics including endoscopic and histological definitions of BE and early EAC; prevalence, incidence, natural history, and risk factors for BE; and methods for managing BE and early EAC. The latter considered modification of lifestyle factors; screening and surveillance strategies; and medical, endoscopic, and surgical interventions. To answer each question, the working party systematically reviewed the literature and developed a set of recommendations through consensus. Evidence underpinning each recommendation was rated according to quality and applicability.

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.

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.

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.

Additive impact of pre-liver transplant metabolic factors on survival post-liver transplant.

Diabetes at time of liver transplantation is associated with reduced post‐transplant survival. We aimed to assess whether additional metabolic conditions such as obesity or hypertension had additive prognostic impact on post‐transplantation survival.

Standardised reporting protocol for endoscopic resection for Barrett oesophagus associated neoplasia: expert consensus recommendations

Summary Endoscopic resection (ER) is considered the therapy of choice for intraepithelial neoplasia associated with visible lesions and T1a adenocarcinoma. Pathologists are bound to encounter specimens collected via these techniques more frequently in their practice. A standardised protocol for handling, grossing, and assessing ER specimens should be adopted to ensure that all prognostic information and characteristics influencing treatment are included in reports (see Supplementary Video Abstract, http://links.lww.com/PAT/A22). The entire specimen should be appropriately oriented, processed and assessed. An ER specimen will commonly show intraepithelial neoplasia or invasive carcinoma. There are essential features that should be recorded if invasive carcinoma is found as they dictate further management and follow-up. These features are the margin status, depth of invasion, degree of differentiation and presence or absence of lymphovascular invasion. Important features such as duplication of muscularis mucosae should be recognised to avoid misinterpretation of depth of invasion. Key diagnostic and prognostic elements that are essential for optimal clinical decisions have been included in the reporting format proposed by the Structured Pathology Reporting committee of the Royal College of Pathologists of Australasia (RCPA).