Expert assessment of infiltration depth and recommendation of endoscopic resection technique in early Barrett cancer.

BACKGROUND: Early Barrett cancer can be curatively treated by endoscopic resection. The choice of the resection technique, however-endoscopic mucosal resection (EMR) or submucosal dissection (ESD)-largely depends on the assumed infiltration depth as judged by the endoscopist. However, the accuracy of endoscopic diagnosis of the degree of cancer infiltration is not known. METHODS: Three to four high-quality images (both in overview and close-up) from 202 of early Barrett esophagus cancer cases (82% men, mean age 66.9 years) were selected from our endoscopy database (73.3% stage T1a and 26.7% in stage T1b). Images were shown to 9 Barrett esophagus experts, with patients' clinical data (age, sex, Barrett esophagus length) and biopsy results. The experts were asked to predict infiltration depth (T1b vs. T1a), and to suggest the appropriate endoscopic resection technique (EMR or ESD, or surgery). Interobserver variability (kappa values) was also determined for these parameters. RESULTS: Overall positive (PPV) and negative predictive values (NPV) to diagnose T1b versus T1a infiltration were 40.7% (95% CI: 36.7, 44.8) and 79.8% (95% CI: 77.5, 81.9), respectively; kappa value was 0.41. Paris classification (kappa 0.51) and suggested treatment also varied between experts. In a post hoc analysis, only the correlation between lesions classified as invisible or flat according to the Paris classification (IIB; 25% of all cases) and the suggested resection technique was better: In this subgroup, EMR was recommended in >80% of cases, with a high complete (basal R0) resection rate (mean of 88.1%). CONCLUSIONS: Precise endoscopic distinction between mucosal and submucosal involvement of Barrett esophagus cancer by experts as a basis for choosing the resection technique has limited predictive values and high interobserver variability. It seems that mainly invisible/flat lesions may result in good resection outcomes when treated by EMR, but this stratification strategy has to be assessed in further studies.

Second-generation distal attachment cuff for adenoma detection in screening colonoscopy: a randomized multicenter study.

BACKGROUND AND AIMS: Randomized studies have demonstrated that a distal attachment cap with rubber side arms, the Endocuff Vision (ECV; Olympus America, Center Valley, Pa, USA), increased colonoscopic adenoma detection rate (ADR) in various mixed patient collectives. This is the first study to evaluate its use in a primary colonoscopic screening program. METHODS: Patients over age 55 years undergoing screening colonoscopy in 9 German private offices in Berlin and Hamburg were randomized to either the study group using ECV or the control group using high-definition colonoscopies (standard of care). The main outcome parameter was ADR, whereas secondary outcomes were detection rates of all adenomas per colonoscopy (APCs), of adenoma subgroups, and of hyperplastic polyps. RESULTS: Of 1416 patients (mean age, 61.1 years; 51.8% women), with a median of 41 examinations per examiner (n = 23; interquartile range, 12-81), 700 were examined with ECV and 716 without. Adjusting for the effects of the colonoscopies, ADR was 39.5% (95% confidence interval [CI], 32.6%-46.3%) in the ECV group versus 32.2% (95% CI, 25.9%-38.6%) in the control group, which resulted in an increase of 7.2% (95% CI, 2.3%-12.2%; P = .004). The increase in ADR was mainly because of small polyps, with adjusted ADRs for adenomas <10 mm of 33.3% (95% CI, 26.5%-40.2%) for study patients versus 24.0% (95% CI, 18.2%-29.8%) for control patients (P < .001). APC was also significantly increased (.57 ECV vs .51 control subjects, P = .045). CONCLUSIONS: A distal attachment cap with side arms significantly increased the ADR in patients undergoing primary colonoscopic screening. Because of the correlation of ADR and interval cancer, its use should be encouraged, especially in this setting. (Clinical trial registration number: NCT03442738.).

Designs of colonoscopic adenoma detection trials: more positive results with tandem than with parallel studies - an analysis of studies on imaging techniques and mechanical devices.

BACKGROUND AND AIMS: Adenoma detection rate (ADR) has been shown to correlate with interval cancers after screening colonoscopy and is commonly used as surrogate parameter for its outcome quality. ADR improvements by various techniques have been studied in randomised trials using either parallel or tandem methodololgy. METHODS: A systematic literature search was done on randomised trials (full papers, English language) on tandem or parallel studies using either adenoma miss rates (AMR) or ADR as main outcome to test different novel technologies on imaging (new endoscope generation, narrow band imaging, iScan, Fujinon intelligent chromoendoscopy/blue laser imaging and wide angle scopes) and mechanical devices (transparent caps, endocuff, endorings and balloons). Available meta analyses were also screened for randomised studies. RESULTS: Overall, 24 randomised tandem trials with AMR (variable definitions and methodology) and 42 parallel studies using ADR (homogeneous methodology) as primary outcome were included. Significant differences in favour of the new method were found in 66.7% of tandem studies (8222 patients) but in only 23.8% of parallel studies (28 059 patients), with higher rates of positive studies for mechanical devices than for imaging methods. In a random-effects model, small absolute risk differences were found, but these were double in magnitude for tandem as compared with parallel studies (imaging: tandem 0.04 (0.01, 0.07), parallel 0.02 (0.00, 0.04); mechanical devices: tandem 0.08 (0.00, 0.15), parallel 0.04 (0.01, 0.07)). Nevertheless, 94.2% of missed adenomas in the tandem studies were small (<1 cm) and/or non-advanced. CONCLUSIONS: A tandem study is more likely to yield positive results than a simple parallel trial; this may be due to the use of different parameters, variable definitions and methodology, and perhaps also a higher likelihood of bias. Therefore, we suggest to accept positive results of tandem studies only if accompanied by positive results from parallel trials.

Right-Sided Location Not Associated With Missed Colorectal Adenomas in an Individual-Level Reanalysis of Tandem Colonoscopy Studies.

BACKGROUND & AIMS: Interval cancers occur more frequently in the right colon. One reason could be that right-sided adenomas are frequently missed in colonoscopy examinations. We reanalyzed data from tandem colonoscopies to assess adenoma miss rates in relation to location and other factors. METHODS: We pooled data from 8 randomized tandem trials comprising 2218 patients who had diagnostic or screening colonoscopies (adenomas detected in 49.8% of patients). We performed a mixed-effects logistic regression with patients as cluster effects with different independent parameters. Factors analyzed included location (left vs right, splenic flexure as cutoff), adenoma size, form, and histologic features. Analyses were controlled for potential confounding factors such as patient sex and age, colonoscopy indication, and bowel cleanliness. RESULTS: Right-side location was not an independent risk factor for missed adenomas (odds ratio [OR] compared with the left side, 0.94; 95% CI, 0.75-1.17). However, compared with adenomas ≤5 mm, the OR for missing adenomas of 6-9 mm was 0.62 (95% CI, 0.44-0.87), and the OR for missing adenomas of ≥10 mm was 0.51 (95% CI, 0.33-0.77). Compared with pedunculated adenomas, sessile (OR, 1.82; 95% CI, 1.16-2.85) and flat adenomas (OR, 2.47; 95% CI, 1.49-4.10) were more likely to be missed. Histologic features were not significant risk factors for missed adenomas (OR for adenomas with high-grade intraepithelial neoplasia, 0.68; 95% CI, 0.34-1.37 and OR for sessile serrated adenomas, 0.87; 95% CI, 0.47-1.64 compared with low-grade adenomas). Men had a higher number of adenomas per colonoscopy (1.27; 95% CI, 1.21-1.33) than women (0.86; 95% CI, 0.80-0.93). Men were less likely to have missed adenomas than women (OR for missed adenomas in men, 0.73; 95% CI, 0.57-0.94). CONCLUSIONS: In an analysis of data from 8 randomized trials, we found that right-side location of an adenoma does not increase its odds for being missed during colonoscopy but that adenoma size and histologic features do increase risk. Further studies are needed to determine why adenomas are more frequently missed during colonoscopies in women than men.

Extended cycle streptozotocin/5-FU chemotherapy for maintenance therapy in pancreatic neuroendocrine tumors.

PURPOSE: The standard of care treatment for patients with advanced pancreatic neuroendocrine tumors (pNET) is a combination of streptozotocin and 5-FU. Although widely used, little is known about the best long-term strategy with these substances. METHODS: We here report our experience of 28 patients treated with streptozotocin/5-FU for advanced pNET with special consideration for long-term management using an extended cycle protocol. RESULTS: Standard 6-weekly Moertel protocol resulted in a median progression-free survival of 21 months (range 3-128) and a median overall survival of 69 months (range 3-157+) in the whole cohort. Thirteen of the 28 patients were switched to an extended 3-month cycle protocol for maintenance therapy. Of these 13 patients, 2 achieved complete remission, 1 partial remission, and 8 stable disease as best response while 2 showed progressive disease following switch to the extended protocol, resulting in an additional median progression-free survival of 23 months. Median overall survival after the start of chemotherapy in this patient group was 69 months (21-157+). Patients benefitted from extended periods free of chemotherapy-associated side effects after switching to the extended cycle protocol. CONCLUSIONS: Switching to an extended cycle protocol of 3 months for maintenance therapy following initial standard cycles may achieve long-term disease stabilization in selected patients with advanced pNET with good patient acceptance.

Effects of two instrument-generation changes on adenoma detection rate during screening colonoscopy: results from a prospective randomized comparative study.

BACKGROUND: Previous studies have shown that multiple colonoscope features have to be changed before an improvement in adenoma detection rate (ADR) becomes obvious, such as with changing from one instrument generation to the next but one. We wanted to evaluate whether such an effect can also be observed in a private-practice screening setting. METHODS: In a randomized study, we compared the latest generation colonoscopes from one company (Olympus Exera III, 190) with the next to last one (Olympus 165), including only patients presenting for screening colonoscopy. The primary outcome was ADR achieved with 190 colonoscopes (190-C) in comparison with 165 colonoscopes (165-C). RESULTS: 1221 patients (46.1 % men; mean age 62.2 years, standard deviation 6.6) were included (599 screened with the Olympus Exera III, 190). The ADR difference in favor of the 190-C instrument (32 % [95 % confidence interval (CI) 26 % to 39 %] vs. 28 % [95 %CI 22 % to 34 %] in the 165-C group) failed to reach statistical significance (P = 0.10); only the rate of small (< 5 mm) adenomas was significantly increased at 22.5 % (95 %CI 19 % to 26 %) vs. 15.6 % (95 %CI 13 % to 18 %; P = 0.002). Furthermore, significantly more adenomas were found in the 190-C group, with an adenoma rate (all adenomas/all patients) of 0.57 (95 %CI 0.53 to 0.61) vs. 0.47 (95 %CI 0.43 to 0.51; P < 0.001). CONCLUSIONS: This randomized comparative trial in a private-practice screening setting only partially confirmed the results of prior studies that, with multiple imaging improvements achieved over two instrument generations, an increase in overall adenoma number becomes measurable.

Risk of Malignancy in Adenomas Detected During Screening Colonoscopy.

BACKGROUND & AIMS: A higher incidence of proximal interval cancers after colonoscopy has been reported in several follow-up studies. One possible explanation for this might be that proximally located adenomas have greater malignant potential. The aim of the present study was to assess the risk of malignancy in proximal versus distal adenomas in patients included in a large screening colonoscopy database; adenoma shape and the patients' age and sex distribution were also analyzed. METHODS: Data for 2007-2012 from the German National Screening Colonoscopy Registry, including 594,614 adenomas identified during 2,532,298 screening colonoscopies, were analyzed retrospectively. The main outcome measure was the rate of high-grade dysplasia (HGD) in adenomas, used as a surrogate marker for the risk of malignancy. Odds ratios (ORs) for the rate of HGD found in adenomas were analyzed in relation to patient- and adenoma-related factors using multivariate analysis. RESULTS: HGD histology was noted in 20,873 adenomas (3.5%). Proximal adenoma locations were not associated with a higher HGD rate. The most significant risk factor for HGD was adenoma size (OR 10.36 ≥1 cm vs <1 cm), followed by patient age (OR 1.26 and 1.46 for age groups 65-74 and 75-84 vs 55-64 years) and sex (OR 1.15 male vs female). In comparison with flat adenomas as a reference lesion, sessile lesions had a similar HGD rate (OR 1.02) and pedunculated adenomas had a higher rate (OR 1.23). All associations were statistically significant (P ≤ .05). CONCLUSIONS: In this large screening database, it was found that the rates of adenomas with HGD are similar in the proximal and distal colon. The presence of HGD as a risk marker alone does not explain higher rates of proximal interval colorectal cancer. We suggest that certain lesions (flat, serrated lesions) may be missed in the proximal colon and may acquire a more aggressive biology over time. A combination of endoscopy-related factors and biology may therefore account for higher rates of proximal versus distal interval colorectal cancer.

Expert opinions and scientific evidence for colonoscopy key performance indicators.

Colonoscopy is a widely performed procedure with procedural volumes increasing annually throughout the world. Many procedures are now performed as part of colorectal cancer screening programmes. Colonoscopy should be of high quality and measures of this quality should be evidence based. New UK key performance indicators and quality assurance standards have been developed by a working group with consensus agreement on each standard reached. This paper reviews the scientific basis for each of the quality measures published in the UK standards.