Michael Greenspan

Advanced adenoma detection rate is independent of nonadvanced adenoma detection rate.

OBJECTIVES:Adenoma detection rate (ADR) is the accepted rate marker in colonoscopy quality. Advanced adenomas detected at index colonoscopy, while less frequent than nonadvanced adenomas, carry greater risk for future advanced neoplasia during surveillance colonoscopy. This study aimed to determine the effect of the colonoscopist and other factors on advanced ADR and to define the correlation of advanced and nonadvanced ADRs among colonoscopists.METHODS:An observational study of a cohort of patients undergoing first-time colorectal cancer screening colonoscopy was conducted. Patient characteristics and colonoscopic findings were collected. Adenoma, advanced adenoma, and nonadvanced ADRs were calculated. Logistic regression was used to determine variable effects on advanced adenoma detection, and Spearmans rank-order correlation was used to evaluate the relationship between advanced and nonadvanced ADRs.RESULTS:A total of 1,944 patients had first-time screening colonoscopies by 14 colonoscopists. All colonoscopists had adequate (>20%) ADRs. The variability in the colonoscopist ranges of detection was 22.22 to 44.66% for adenomas and 2.00 to 18.18% for advanced adenomas. Logistic regression showed that increasing patient age (odds ratio (OR) 1.16 per 5-year increase, 95% confidence interval (CI) 1.05–1.28, P=0.008) and male gender (OR 2.15, 95% CI 1.51–3.06, P<0.0001) were variables associated with advanced adenoma detection. Colonoscopists were significantly different in detecting advanced adenomas by random effects model (P=0.002), adjusting for patient age, gender, race, year of colonoscopy, gastroenterology fellow participation during colonoscopy, and nonadvanced adenomas. Spearmans rank-order correlation coefficient of −0.42 (95% CI −0.77 to 0.14, P=0.13) was not significant and showed no correlation between advanced and nonadvanced adenoma detection by the group of colonoscopists.CONCLUSIONS:Advanced ADR is variable among colonoscopists with acceptable ADRs. Colonoscopists’ advanced ADRs are independent of their nonadvanced ADRs.

Commonality and differences of methylation signatures in the plasma of patients with pancreatic cancer and colorectal cancer

Profiling of DNA methylation status of specific genes is a way to screen for colorectal cancer (CRC) and pancreatic cancer (PC) in blood. The commonality of methylation status of cancer‐related tumor suppressor genes between CRC and PC is largely unknown. Methylation status of 56 cancer‐related genes was compared in plasma of patients in the following cohorts: CRC, PC and healthy controls. Cross validation determined the best model by area under ROC curve (AUC) to differentiate cancer methylation profiles from controls. Optimal preferential gene methylation signatures were derived to differentiate either cancer (CRC or PC) from controls. For CRC alone, a three gene signature (CYCD2, HIC and VHL) had an AUC 0.9310, sensitivity (Sens) = 0.826, specificity (Spec) = 0.9383. For PC alone, an optimal signature consisted of five genes (VHL, MYF3, TMS, GPC3 and SRBC), AUC 0.848; Sens = 0.807, Spec = 0.666. Combined PC and CRC signature or “combined cancer signature” was derived to differentiate either CRC and PC from controls (MDR1, SRBC, VHL, MUC2, RB1, SYK and GPC3) AUC = 0.8177, Sens = 0.6316 Spec = 0.840. In a validation cohort, N = 10 CRC patients, the optimal CRC signature (CYCD2, HIC and VHL) had AUC 0.900. In all derived signatures (CRC, PC and combined cancer signature) the optimal panel used preferential VHL methylation. In conclusion, CRC and PC differ in specific genes methylated in plasma other than VHL. Preferential methylation of VHL is shared in the optimal signature for CRC alone, PC alone and combined PC and CRC. Future investigations may identify additional methylation markers informative for the presence of both CRC and PC.

Dysplasia detection rate of confirmatory EGD in nondysplastic Barrett's esophagus.

Current guidelines for endoscopic surveillance of Barretts esophagus (BE) recommend that patients with newly diagnosed BE undergo confirmatory esophagogastroduodenoscopy (EGD) to exclude the presence of dysplasia. The extent to which confirmatory endoscopy alters management and detects missed dysplasia in newly diagnosed BE has not been reported. The frequency with which confirmatory endoscopy changed surveillance management in patients with newly diagnosed BE was assessed. A two center cohort analysis was conducted on patients newly diagnosed with BE. The rate of dysplasia on confirmatory endoscopy for patients who had nondysplastic BE was obtained. Demographic and endoscopic variables were assessed for association with dysplasia detection using Firth logistic regression model. Out of the 146 patients newly diagnosed with BE and initially determined to be without dysplasia, 12 had dysplasia on the confirmatory second EGD (8.2%). Eleven of 12 cases with dysplasia on confirmatory endoscopy had long-segment BE (LSBE). Among all the LSBE cases in our cohort, 11 had newly diagnosed dysplasia on confirmatory EGD, 29.7% (11/37). The average number of biopsies obtained from the 11 LSBE cases with dysplasia was comparable with the rest of the LSBE cases without dysplasia (6.73 and 5.42, respectively, P-value 0.205). The rate of dysplasia detection in short-segment BE (SSBE) was much lower, 0.95% (1 out of 105). There were no cases of high-grade dysplasia (HGD) or cancer detected in any SSBE case. HGD was detected on confirmatory EGD in two cases, both were LSBE. Segment length was the only statistically significant factor to predict the presence of dysplasia on confirmatory endoscopy (odds ratio 9.158, P. 0.008). Confirmatory EGD in newly diagnosed LSBE had significant rate of dysplasia detection (29.7%) in this cohort. Among patients with SSBE, there was a low rate of dysplasia detection with confirmatory EGD, less than 1% of cases. No additional cases of HGD or esophageal carcinoma in SSBE cases were detected. This suggests that the yield of confirmatory EGD is greater in patients with LSBE.

Negative surveillance endoscopy occurs frequently in patients with short-segment non-dysplastic Barrett's esophagus.

Surveillance endoscopy of non-dysplastic Barretts esophagus (NDBE) that fails to detect intestinal metaplasia (IM), or negative surveillance, is known to occur in clinical practice, although the frequency and possible outcomes in a large cohort in clinical practice is not well described. The goals of this study were to define frequency in which negative surveillance occurs and endoscopic outcomes in a screening cohort of short segment NDBE. A retrospective cohort (n = 184) of patients newly diagnosed with short segment NDBE at an outpatient academic tertiary care center between 2003 and 2011 were reviewed. Only those with one or more surveillance endoscopies were included to define a frequency of negative surveillance. Included patients were further assessed if they had two or more surveillance endoscopies and were classified into groups as sampling error or negative IM on consecutive surveillances based on the results of their surveillance endoscopies. The frequency of a negative surveillance endoscopy in all short-segment NDBE patients was 19.66% (92 endoscopic exams were negative for IM of 468 total surveillance exams). A negative surveillance endoscopy occurred in 40.76% (n = 75) patients. Sampling error occurred in 44.12% and negative IM on consecutive surveillance endoscopies in 55.88% of those with ≥ 2 surveillance endoscopies and an initially negative surveillance exam. The frequency of negative IM on consecutive surveillances was 19.00% of all patients who had two surveillance endoscopies. When the index diagnostic Barretts esophagus segment length was < 1 cm, 32.14% (18/56) of all patients (with ≥ 2 surveillance endoscopies) had negative IM on consecutive surveillance endoscopies. Negative surveillance occurs frequently in short-segment NDBE. When an initial negative surveillance endoscopy occurs, it may be due to either a sampling error or lack of detectable IM on surveillance exam. When a <1 cm segment of NDBE is diagnosed, a significant proportion of patients may go on to have continuously undetected IM on consecutive surveillance endoscopic exams without intervention.

Seeking the Cecum: Assessing Metrics in Fellow Procedural Training

The ability to independently perform colonoscopy is a fundamental milestone of gastroenterology fellowship training due to the need to learn the many technical and cognitive elements required to master the procedure [1–3]. Although the field has historically relied heavily on the important metric of cecal intubation as a marker of proficiency in the assessment of trainees [3], there are limitations specific to this metric. First, the ability to intubate the cecum may not correlate with multiple other important procedural skills needed for competency, such as polyp identification and resection, in addition to cognitive skills such as those required to achieve safe sedation and ensure patient comfort and safety [4]. Second, there is wide variation in the number of procedures needed for trainees to perform in order to achieve technical proficiency in cecal intubation, as defined by the metric of C90 % success [1, 2, 5]. Furthermore, the numerical threshold for competence is the completion of 140 colonoscopies, a figure based on a single study of 35 trainees, which has since been shown to be a gross underestimate of the number of procedures for colonoscopy proficiency. Thus, proposing a ‘‘one-size-fits-all’’ number of procedures for trainees is puzzling. In this issue of Digestive Diseases and Sciences, McCarthy and colleagues report a correlation between early mastery of splenic flexure intubation and the ability to achieve consistent cecal intubation [6]. Their findings, which detail an important aspect of colonoscopic competency, may help improve endoscopic training beyond a historical ‘‘one-size-fits-all’’ model, tailoring individual colonoscopic training to individual abilities and competencies. The median number of procedures required for trainees to achieve a splenic flexure intubation rate (SFIR) C90 % was 37 colonoscopies. The main finding of the study is that the mean number of colonoscopies to achieve a cecal intubation rate (CIR) C90 % was lower at 208 procedures than the 352 procedures (standard deviation = 115) needed to achieve splenic flexure intubation earlier, findings that are somewhat intuitive in that mastery of left colon intubation is one of the most difficult aspects of colonoscopic technique [7]. This is a well-designed study that has practical application in identifying those trainees who will consistently obtain satisfactory cecal intubation rates more rapidly, potentially identifying those who are struggling early on in their training, prompting the institution of interventions for ‘‘late learners’’ that may potentially shorten their learning curve. Limitations of this retrospective single center study include a discussion of how suboptimal bowel preparations may impact SFIR. Furthermore, as the authors note, patient factors including demographic data are not accounted for. In this study, 66 % of procedures were performed in at a typically male-predominant Veteran Affairs hospital. The findings may be skewed toward the technically easier colonoscopies in men and may be a limiting factor in applicability to training programs with more gender neutral or female-predominant patient populations [8]. Lastly, a lack of standardization of the teaching method is a potential flaw. Despite these limitations, the findings are exciting in that early training information can help predict the course of achieving reliable cecal intubation proficiency, & Michael Greenspan Michael_Greenspan@rush.edu