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.

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.

Cost Analysis of Endoscopic Mucosal Resection vs Surgery for Large Laterally Spreading Colorectal Lesions.

BACKGROUND & AIMS: Large laterally spreading lesions (LSL) in the colon and rectum can be safely and effectively removed by endoscopic mucosal resection (EMR). However, many patients still undergo surgery. Endoscopic treatment may be more cost effective. We compared the costs of endoscopic versus surgical management of large LSL. METHODS: We performed a prospective, observational, multicenter study of consecutive patients referred to 1 of 7 academic hospitals in Australia for the management of large LSL (≥ 20 mm) from January 2010 to December 2013. We collected data on numbers of patients undergoing EMR, actual endoscopic management costs (index colonoscopy, hospital stay, adverse events, and first surveillance colonoscopy), characteristics of patients and lesions, outcomes, and adverse events, and findings from follow-up examinations 14 days, 4-6 months, and 16-18 months after treatment. We compared data from patients who underwent EMR with those from a model in which all patients underwent surgery without any complications. Event-specific costs, based on Australian refined diagnosis-related group codes, were used to estimate average cost per patient. RESULTS: EMR was performed on 1489 lesions (mean size, 36 mm) in 1353 patients (mean age, 67 years; 52.1% male). Total costs involved in the endoscopic management of large LSL were US $6,316,593 and total inpatient hospitalization length of stay was 1180 days. The total cost predicted for the surgical management group was US $16,601,502, with a total inpatient hospitalization length of stay of 4986 days. Endoscopic management produced a potential total cost saving of US $10,284,909; the mean cost difference per patient was US $7602 (95% confidence interval, $8458-$9220; P < .001). Inpatient hospitalization length of stay was reduced by 2.81 nights per patient (95% confidence interval, 2.69-2.94; P < .001). CONCLUSIONS: In a large multicenter study, endoscopic management of large LSL by EMR was significantly more cost-effective than surgery. Endoscopic management by EMR at an appropriately experienced and resourced tertiary center should be considered the first line of therapy for most patients with this disorder. This approach is likely to deliver substantial overall health expenditure savings. ClinicalTrials.gov, Number: NCT01368289.

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.

Risk factors for intraprocedural and clinically significant delayed bleeding after wide-field endoscopic mucosal resection of large colonic lesions.

BACKGROUND & AIMS: Wide-field endoscopic mucosal resection (WF-EMR) of large sessile colonic polyps is a safe and cost-effective outpatient treatment. Bleeding is the main complication. Few studies have examined risk factors for bleeding during the procedure (intraprocedural bleeding [IPB]) or after it (clinically significant post-endoscopic bleeding [CSPEB]). We investigated factors associated with IPB and CSPEB in a large prospective study. METHODS: We analyzed data from WF-EMRs of sessile colorectal polyps ≥ 20 mm in size (mean size, 35.5 mm), which were performed on 1172 patients (mean age, 67.8 years) from June 2008-March 2013 at 7 tertiary hospitals as part of the Australian Colonic Endoscopic Resection Study. Data were collected on characteristics of patients and lesions, along with outcomes of procedures and clinical and histologic analyses. Independent predictors of IPB and CSPEB were identified by multiple logistic regression analysis. RESULTS: Of the patients studied, 133 (11.3%) had IPB. Independent predictors included increasing lesion size (odds ratio, 1.24/10 mm; P < .001), Paris endoscopic classification of 0-IIa + Is (odds ratio, 2.12; P = .004), tubulovillous or villous histology (odds ratio, 1.84; P = .007), and study institutions that performed the procedure on fewer than 75 patients (odds ratio, 3.78; P < .001). All IPB was successfully controlled endoscopically. IPB prolonged procedures and was associated with early recurrence (relative risk, 1.68; P = .011). Seventy-three patients (6.2%) had CSPEB. On multivariable analysis, CSPEB was associated with proximal colon location (odds ratio, 3.72; P < .001), use of an electrosurgical current not controlled by a microprocessor (odds ratio, 2.03; P = .038), and IPB (odds ratio, 2.16; P = .016). Lesion size and comorbidities did not predict CSPEB. CONCLUSIONS: In a prospective study of patients undergoing WF-EMR of large sessile colonic polyps, IPB is associated with larger lesions, lesion histology, and Paris endoscopic classification of type 0-IIa + Is. IPB prolongs the duration of the procedure, is a marker for recurrence, and is associated with CSPEB. CSPEB occurs most frequently in the proximal colon and less when current is controlled by a microprocessor.

A management algorithm based on delayed bleeding after wide-field endoscopic mucosal resection of large colonic lesions.

BACKGROUND & AIMS: Bleeding is the main complication of wide-field endoscopic mucosal resection (WF-EMR) for large colonic lesions. Few studies have examined bleeding outcomes after WF-EMR, and there are no evidence-based guidelines for management of bleeding in this group. We analyzed outcomes of patients with clinically significant post-EMR bleeding (CSPEB) and present a management algorithm based on our findings. METHODS: In a prospective study, we collected data from WF-EMR of sessile colorectal polyps 20 mm or larger from 1039 patients who participated in the Australian Colonic Endoscopic resection multicenter study from July 2008 through May 2012. Data included patient and lesion characteristics and procedural, clinical, and histologic outcomes. Patients participated in a structured telephone interview 14 days after the procedure; independent predictors of a moderate or severe outcome by American Society of Gastrointestinal Endoscopists criteria, or any intervention for hemostasis, were identified. RESULTS: Sixty-two patients had CSPEB (6.0%); 34 were managed conservatively (55%) and 27 underwent colonoscopy (44%). One patient had primary embolization. Endoscopic therapy was applied in 21 cases; 14 had active bleeding. Two of the conservatively managed cases underwent colonoscopy for rebleeding after discharge. On multivariable analysis, moderate or severe bleeding events were associated with hemodynamic instability (odds ratio, 12.3; P = .046) and low level of hemoglobin at presentation (odds ratio, 0.50 per 1.0 g/dL; P = .005). Intervention for hemostasis was associated with hourly or more frequent hematochezia (odds ratio, 36.7; P = .001), American Society of Anesthesiologists grade 2 or higher (odds ratio, 20.1; P < .001), and transfusion (odds ratio, 18.7; P = .003). CONCLUSIONS: Based on a multicenter prospective study, CSPEB resolves spontaneously in 55% of patients. We developed a risk factor-based algorithm that might assist physicians in the management of bleeding. Patients responding to initial resuscitation can be observed, with a lower threshold for intervention in those with the identified risk factors.

Hepatic failure due to fibrosing cholestatic hepatitis in a patient with pre-surface mutant hepatitis B virus and mixed connective tissue disease treated with prednisolone and chloroquine.

Fibrosing cholestatic hepatitis (FCH) is a severe variant of hepatitis B infection that has until recently been described almost exclusively in the setting of organ transplantation and HIV infection. This case report describes a patient with pre-surface (pre-S) mutant hepatitis B virus (HBV) infection who developed a fatal form of FCH after high dose prednisolone for mixed connective tissue disease (MCTD). The role of corticosteroids and pre-S viral mutation in the pathogenesis of the disease is discussed, and the importance of early diagnosis is emphasised. This report alerts the physician to the need for close monitoring of LFTs and HBV DNA of hepatitis B carriers during immunosuppressive therapy regardless of the indication. As in the transplantation setting, viral DNA levels should be kept to undetectable if viral replication or recurrence is to be prevented.

Colonoscopic diagnosis of mucocele of the appendix.

BACKGROUND: Appendiceal mucoceles are uncommon cystic neoplasms characterized by distension of the appendiceal lumen with mucus. There have been no reported series of colonoscopically diagnosed mucoceles with clinicopathologic correlation. METHODS: A retrospective review of colonoscopies performed at our institution over the past 14 years was undertaken with patient demographics, clinical data, surgical outcomes, and histopathology obtained from hospital records. OBSERVATIONS: Seven patients (6 women) with mucocele of the appendix were identified at colonoscopy. Three had complained of right lower quadrant pain. All 7 patients underwent surgical resection. Histopathology demonstrated mucinous cystadenoma in all. No cases revealed carcinoma, and there have been no deaths related to the mucocele. CONCLUSIONS: Appendiceal mucoceles may be recognized at colonoscopy as a smooth bulbous submucosal lesion of the cecum with an impression formed by the appendiceal orifice. Recognition at colonoscopy is important because it enables accurate diagnosis and directs management. Surgery is recommended in all cases given the risk of malignancy or perforation with resultant pseudomyxoma peritonei.

Given capsule endoscopy in celiac disease: evaluation of diagnostic accuracy and interobserver agreement.

BACKGROUND AND AIMS: Capsule endoscopy (CE) has been increasingly used for diagnosing diseases of the small bowel. It is an attractive technique for assessing celiac disease (CD) because it is noninvasive and provides a close and magnified view of the mucosa of the entire small bowel. In this study, we evaluated the accuracy of CE and interobserver agreement in recognizing villous atrophy (VA) using histopathology as the reference. We also explored the extent of small bowel involvement with CD and the relationship between the length of the affected bowel and the clinical presentation. METHODS: Ten CD patients with histologically proven VA and the same number of controls were subjected to CE. Four, blinded to histology findings, investigators (two with and two without prestudy CE experience) were asked to diagnose VA on CE images. RESULTS: Based on assessment of all four investigators, the overall sensitivity, specificity, PPV, and NPV of CE in diagnosing VA were 70%, 100%, 100%, and 77%, respectively. The sensitivity and the specificity of the test was 100% when the reports of experienced capsule endoscopists only were analyzed. The interobserver agreement was perfect (kappa= 1.0) between investigators with prestudy CE experience and poor (kappa= 0.2) between the investigators who had limited prestudy exposure to CE. Celiac patients with extensive small bowel involvement had typical symptoms of malabsorption (diarrhea, weight loss) as opposed to mild and nonspecific symptoms in patients whose disease was limited to the proximal small bowel. CE was tolerated well by all study participants with 95% reporting absence of any discomfort. CONCLUSIONS: Although based on a small sample size, the study suggests that CE may be useful in assessing patients with CD. Familiarity with CE technology appears to be a critical factor affecting the accuracy of the test. Larger studies are warranted to more precisely define the advantages and limitations of CE in CD.