Adenoma Detection Rate (ADR) Irrespective of Indication Is Comparable to Screening ADR: Implications for Quality Monitoring.

BACKGROUND & AIMS: Adenoma detection rate (ADR) is a key measure of colonoscopy quality. However, efficient measurement of ADR can be challenging because many colonoscopies are performed for non-screening purposes. Measuring ADR without being restricted to screening indication may likely facilitate more widespread implementation of quality monitoring. We hypothesized that the ADR for all colonoscopies, irrespective of the indication, would be equivalent to the ADR for screening colonoscopies. METHODS: We reviewed consecutive colonoscopies at two Veterans Affairs centers performed by 21 endoscopists over 6 months in 2015. We calculated the ADR for screening exams, non-screening (surveillance and diagnostic) exams, and all exams (irrespective of indication), correcting for within-endoscopist correlation. We then performed simulation modeling to calculate the ADRs under 16 hypothetical scenarios of various indication distributions. We simulated 100,000 trials with 3,000 participants, randomly assigned indication (screening, surveillance, diagnostic, and FIT+) from a multinomial distribution, randomly drew adenoma using the observed ADRs per indication, and calculated 95% confidence intervals of the mean differences in ADR of screening and non-screening indications. RESULTS: Among 2628 colonoscopies performed by 21 gastroenterologists, the indication was screening in 28.9%, surveillance in 48.2% and diagnostic in 22.9%. There was no significant difference in the ADR, 50% (95%CI: 45-56%) for all colonoscopies vs 49% (95%CI: 43-56%) for screening exams (p=.55). ADRs were 56% for surveillance and 38% for diagnostic exams. In our simulation modeling, only one out of 16 scenarios (screening 10%, surveillance 70%, diagnostic 10% and FIT+ 10%) resulted in a significant difference between the calculated ADRs for screening and non-screening indications. CONCLUSIONS: In our study, the overall ADR computed from all colonoscopies was not significantly different than the conventional ADR based on screening colonoscopies. Assessing ADR for colonoscopy irrespective of indication may be adequate for quality monitoring, and could facilitate the implementation of quality measurement and reporting. Future prospective studies should evaluate the validity of using overall ADR for quality reporting in other jurisdictions before adopting this method in clinical practice.

Impact of observational training on endoscopic mucosal resection outcomes and competency for large colorectal polyps: single endoscopist experience.

Background and study aims Endoscopic mucosal resection (EMR) is standard treatment for large colorectal polyps. However, it is a specialized technique with limited data on the effectiveness of training methods to acquire this skill. The aim of this study was to evaluate the impact of observational training on EMR outcomes and competency in an early-stage endoscopist. Patients and methods A single endoscopist completed comprehensive EMR training, which included knowledge acquisition and direct observation of EMR cases, and proctored supervision, during the third year of gastroenterology fellowship. After training, EMR was independently attempted on 142 consecutive, large (i. e., ≥ 20 mm), non-pedunculated colorectal polyps between July 2014 and December 2017 (mean age 61.7 years; mean polyp size 30.4 mm; en-bloc resection 55 %). Surveillance colonoscopy for evaluation of residual neoplasia was available for 86 % of the cases. Three primary outcomes were evaluated: endoscopic assessment of complete resection, rate of adverse events (AEs), and rate of residual neoplasia on surveillance colonoscopy. Results Complete endoscopic resection was achieved in 93 % of cases, the rates of AEs and residual neoplasia were 7.8 % and 7.3 %, respectively. The rate of complete resection remained stable (at 85 % or greater) with increasing experience while rates of AEs and residual neoplasia peaked and decreased after 60 cases. Conclusions An early-stage endoscopist can acquire the skills to perform effective EMR after completing observational training. At least 60 independent EMRs for large colorectal polyps were required to achieve a plateau for clinically meaningful outcomes.

Risk factors for postpolypectomy bleeding in patients receiving anticoagulation or antiplatelet medications.

BACKGROUND AND AIMS: Balancing the risks for thromboembolism and postpolypectomy bleeding in patients requiring anticoagulation and antiplatelet agents is challenging. We investigated the incidence and risk factors for postpolypectomy bleeding on anticoagulation, including heparin bridge and other antithrombotic therapy. METHODS: We performed a retrospective cohort and case control study at 2 tertiary-care medical centers from 2004 to 2012. Cases included male patients on antithrombotics with hematochezia after polypectomy. Nonbleeding controls were matched to cases 3 to 1 by antithrombotic type, study site, polypectomy technique, and year of procedure. Our outcomes were the incidence and risk factors for postpolypectomy bleeding. RESULTS: There were 59 cases and 174 matched controls. Postpolypectomy bleeding occurred in 14.9% on bridge anticoagulation. This was significantly higher than the overall incidence of bleeding on antithrombotics at 1.19% (95% confidence interval, 0.91%-1.54%) (59/4923). We identified similarly low rates of bleeding in patients taking warfarin (0.66%), clopidogrel (0.84%), and aspirin (0.92%). Patients who bled tended to have larger polyps (13.9 vs 7.3 mm; P < .001) and more polyps ≥2 cm (41% vs 10%; P < .001). Bleeding risk was increased with restarting antithrombotics within 1 week postpolypectomy (odds ratio [OR] 4.50; P < .001), having polyps ≥2 cm (OR 5.94; P < .001), performing right-sided cautery (OR 2.61; P = .004), and having multiple large polyps (OR 2.92; P = .001). Among patients on warfarin, the presence of bridge anticoagulation was an independent risk factor for postpolypectomy bleeding (OR 12.27; P = .0001). CONCLUSION: We conclude that bridge anticoagulation is associated with a high incidence of postpolypectomy bleeding and is an independent risk factor for hemorrhage compared with patients taking warfarin alone. A higher threshold to use bridge anticoagulation should be considered in patients with an elevated bleeding risk.

Optimizing the quality of endoscopy in inflammatory bowel disease: focus on surveillance and management of colorectal dysplasia using interactive image- and video-based teaching.

BACKGROUND AND AIMS: Varying recommendations regarding the detection and management of dysplasia can lead to uncertainty and may impede the uptake of strategies that could improve surveillance in patients with inflammatory bowel disease (IBD). An educational event was held to assist in disseminating the recently published Surveillance for Colorectal Endoscopic Neoplasia Detection and Management in Inflammatory Bowel Disease Patients: International Consensus Recommendations (SCENIC). METHODS: Specialists in IBD and endoscopy led the Optimizing Quality of Endoscopy in IBD course. The American Society for Gastrointestinal Endoscopy (ASGE) organized the course, and the Crohn's and Colitis Foundation of America (CCFA) provided endorsement. One was held in March 2015 at the ASGE Institute for Training and Technology in Chicago, Illinois, and the second in September 2016 preceding the ASGE Endofest in Chandler, Arizona. The program included interactive case-based discussions and didactic presentations on topics including the rationale and current approach of surveillance in IBD; endoscopic characterization and nomenclature of active and quiescent disease; detection of dysplasia during IBD surveillance; role of image-enhanced endoscopy in IBD surveillance, with a focus on chromoendoscopy technique; and management of dysplasia in IBD. Participants were surveyed before and after the course to assess their perspectives and practice. RESULTS: Eighteen presenters or panel members and approximately 92 IBD and endoscopist physician leaders attended the meeting. Most attendees were aged 30 to 49 years (88.1%), had been in practice less than 10 years (89.7%), were from academic medical centers (90.7%), and spent >50% of their time caring for patients with IBD (59.7%). Recommended quality improvements for endoscopy in IBD included the use of endoscopic scoring systems to describe disease activity, the use of a modified Paris classification to characterize visible dysplastic lesions (polypoid, nonpolypoid with description of presence of ulcer and distinct or indistinct borders), the use of chromoendoscopy for dysplasia detection, and the endoscopic removal of visible dysplastic lesions. In the follow-up survey, participants were asked to indicate whether they had changed their practice as a result of attending the course. Ninety-three percent (93%) indicated they had changed their practice. For dysplasia detection, the use of chromoendoscopy increased: 51.7% of respondents reported using chromoendoscopy in most surveillance colonoscopies compared with 34.3% before the course. For dysplasia management, the use of EMR increased for polypoid and nonpolypoid lesions 10 to 20 mm in size; and the referral of dysplastic lesions 20 mm or larger that appeared endoscopically resectable shifted toward removal by an experienced endoscopist. CONCLUSIONS: Evidence-based advances in endoscopy have occurred in the characterization and nomenclature of active and quiescent disease, polypoid and nonpolypoid dysplasia in IBD, and in the detection and management of dysplasia in colonic IBD. Implementation of updated guidelines and recommendations into clinical practice may be facilitated by interactive image- and video-based courses on the topic.

Detection of Sessile Serrated Adenomas in the Proximal Colon Using Wide-Field Fluorescence Endoscopy.

BACKGROUND & AIMS: Many cancers in the proximal colon develop via from sessile serrated adenomas (SSAs), which have flat, subtle features that are difficult to detect with conventional white-light colonoscopy. Many SSA cells have the V600E mutation in BRAF. We investigated whether this feature could be used with imaging methods to detect SSAs in patients. METHODS: We used phage display to identify a peptide that binds specifically to SSAs, using subtractive hybridization with HT29 colorectal cancer cells containing the V600E mutation in BRAF and Hs738.St/Int cells as a control. Binding of fluorescently labeled peptide to colorectal cancer cells was evaluated with confocal fluorescence microscopy. Rats received intra-colonic 0.0086 mg/kg, 0.026 mg/kg, or 0.86 mg/kg peptide or vehicle and morbidity, mortality, and injury were monitored twice daily to assess toxicity. In the clinical safety study, fluorescently labeled peptide was topically administered, using a spray catheter, to the proximal colon of 25 subjects undergoing routine outpatient colonoscopies (3 subjects were given 2.25 µmol/L and 22 patients were given 76.4 µmol/L). We performed blood cell count, chemistry, liver function, and urine analyses approximately 24 hours after peptide administration. In the clinical imaging study, 38 subjects undergoing routine outpatient colonoscopies, at high risk for colorectal cancer, or with a suspected unresected proximal colonic polyp, were first evaluated by white-light endoscopy to identify suspicious regions. The fluorescently labeled peptide (76.4 µmol/L) was administered topically to proximal colon, unbound peptide was washed away, and white-light, reflectance, and fluorescence videos were recorded digitally. Fluorescence intensities of SSAs were compared with those of normal colonic mucosa. Endoscopists resected identified lesions, which were analyzed histologically by gastrointestinal pathologists (reference standard). We also analyzed the ability of the peptide to identify SSAs vs adenomas, hyperplastic polyps, and normal colonic mucosa in specimens obtained from the tissue bank at the University of Michigan. RESULTS: We identified the peptide sequence KCCFPAQ and measured an apparent dissociation constant of Kd = 72 nM and an apparent association time constant of K = 0.174 min-1 (5.76 minutes). During fluorescence imaging of patients during endoscopy, regions of SSA had 2.43-fold higher mean fluorescence intensity than that for normal colonic mucosa. Fluorescence labeling distinguished SSAs from normal colonic mucosa with 89% sensitivity and 92% specificity. The peptide had no observed toxic effects in animals or patients. In the analysis of ex vivo specimens, peptide bound to SSAs had significantly higher mean fluorescence intensity than to hyperplastic polyps. CONCLUSIONS: We have identified a fluorescently labeled peptide that has no observed toxic effects in animals or humans and can be used for wide-field imaging of lesions in the proximal colon. It distinguishes SSAs from normal colonic mucosa with 89% sensitivity and 92% specificity. This targeted imaging method might be used in early detection of premalignant serrated lesions during routine colonoscopies. ClinicalTrials.gov ID: NCT02156557.

Does Better Specimen Orientation and a Simplified Grading System Promote More Reliable Histologic Interpretation of Serrated Colon Polyps in the Community Practice Setting? Results of a Nationwide Study.

INTRODUCTION: Colonoscopic surveillance guidelines for serrated polyps (SPs) are predicated upon the histologic characteristics of the index polyp. However, discrimination between SP subtypes [hyperplastic polyps vs. sessile serrated adenoma/polyps (SSA/P)] is often unreliable. MATERIALS AND METHODS: We studied the impact of (1) a novel tissue orientation method, performed in the endoscopy laboratory, whereby polyps are flattened in a small paper envelope immediately after resection (modified protocol); and (2) 2012 consensus-modified criteria (CM-2012). These interventions were compared with conventional tissue-handling protocol (CP) and traditional 2008 World Health Organization criteria (WHO). Twenty blinded community pathologists from around the United States scored 100, independent, 0.5 to 2.0 cm, proximal colonic SPs randomly selected from a 2-site tissue section archive. We compared interobserver agreement and diagnostic grading. RESULTS: Interobserver agreement was higher using CM-2012 than WHO criteria (absolute agreement: 13% vs. 4%, P<0.01; 75% agreement: 54% vs. 38%, P<0.01). Interobserver agreement was higher with the modified protocol than with CP (WHO absolute agreement: 6% vs. 2%, P>0.05; WHO 75% agreement: 46% vs. 30%, P>0.05, and CM-2012 absolute agreement: 20% vs. 6%, P=0.07; CM-2012 75% agreement: 66% vs. 42%, P=0.03). Compared with WHO, use of CM-2012 criteria resulted in fewer diagnoses of "indeterminate"; more diagnoses of SSA/P (P<0.01); and "upgraded" the diagnosis from hyperplastic polyps to SSA/P in approximately 7% of cases. These observations were independent of polyp size, patient gender, and study site. CONCLUSIONS: Simple enhancements to postresection SP handling and diagnostic criteria markedly improve interobserver agreement of SP diagnosis among nongastrointestinal community pathologists. This finding, if confirmed, has important implications for SP colonoscopy surveillance guidelines.

A simple tissue-handling technique performed in the endoscopy suite improves histologic section quality and diagnostic accuracy for serrated polyps.

BACKGROUND AND STUDY AIMS: Surveillance intervals after colonoscopic resection of serrated polyps are partially predicated on the histology of the polyp(s) removed during the index exam. Histologic discrimination between sessile serrated adenomas/polyps (SSA/P) and hyperplastic polyps is challenging. We devised and tested a simple tool--an envelope--that gastroenterologists can integrate into routine colonoscopy practice to address this problem. METHODS: In the "modified protocol," immediately after polypectomy each serrated polyp was flattened and enclosed in a paper envelope before being placed in formalin. In the pathology laboratory, each polyp was sectioned after processing. A two-site, prospective, randomized, single-blinded trial was performed to compare this modified protocol with the conventional protocol. Serrated polyps located proximal to the splenic flexure and 5-20 mm in diameter were included. A novel orientation score that measured the number of well-oriented crypts per unit area of polyp (higher orientation score = better orientation) was validated. Orientation score, SSA/P diagnosis rate, and inter-pathologist agreement were measured. RESULTS: A total of 375 polyps were enrolled, of which 264 were identified for analysis. The mean orientation scores in the modified and conventional protocol groups were 3.11 and 1.13, respectively (P < 0.0001). SSA/Ps were diagnosed in 103/135 cases (76.3%) in the modified protocol group vs. 54/129 (41.9%) in the conventional protocol group (P < 0.0001). Inter-pathologist agreement was higher with the modified than the conventional protocol (77.0% vs. 62.8%; P = 0.015). CONCLUSION: Standard polyp handling techniques may be sub-optimal for interpretation of serrated polyps resected at colonoscopy, and may lead to inadvertent histologic "under-grading" of many lesions. Our intervention improved histopathologic interpretation and increased the SSA/P diagnosis rate.

Endoscopic prediction of deep submucosal invasive carcinoma: validation of the narrow-band imaging international colorectal endoscopic (NICE) classification.

BACKGROUND: A simple endoscopic classification to accurately predict deep submucosal invasive (SM-d) carcinoma would be clinically useful. OBJECTIVE: To develop and assess the validity of the NBI international colorectal endoscopic (NICE) classification for the characterization of SM-d carcinoma. DESIGN: The study was conducted in 4 phases: (1) evaluation of endoscopic differentiation by NBI-experienced colonoscopists; (2) extension of the NICE classification to incorporate SM-d (type 3) by using a modified Delphi method; (3) prospective validation of the individual criteria by inexperienced participants, by using high-definition still images without magnification of known histology; and (4) prospective validation of the individual criteria and overall classification by inexperienced participants after training. SETTING: Japanese academic unit. MAIN OUTCOME MEASUREMENTS: Performance characteristics of the NICE criteria (phase 3) and overall classification (phase 4) for SM-d carcinoma; sensitivity, specificity, predictive values, and accuracy. RESULTS: We expanded the NICE classification for the endoscopic diagnosis of SM-d carcinoma (type 3) and established the predictive validity of its individual components. The negative predictive values of the individual criteria for diagnosis of SM-d carcinoma were 76.2% (color), 88.5% (vessels), and 79.1% (surface pattern). When any 1 of the 3 SM-d criteria was present, the sensitivity was 94.9%, and the negative predictive value was 95.9%. The overall sensitivity and negative predictive value of a global, high-confidence prediction of SM-d carcinoma was 92%. Interobserver agreement for an overall SM-d carcinoma prediction was substantial (kappa 0.70). LIMITATIONS: Single Japanese center, use of still images without prospective clinical evaluation. CONCLUSION: The NICE classification is a valid tool for predicting SM-d carcinomas in colorectal tumors.

Narrow band imaging to differentiate neoplastic and non-neoplastic colorectal polyps in real time: a meta-analysis of diagnostic operating characteristics.

PURPOSE: Many studies have reported on the use of narrow band imaging (NBI) colonoscopy to differentiate neoplastic from non-neoplastic colorectal polyps. It has potential to replace pathological diagnosis of diminutive polyps. We aimed to perform a systematic review and meta-analysis on the real-time diagnostic operating characteristics of NBI colonoscopy. METHODS: We searched PubMed, SCOPUS and Cochrane databases and abstracts. We used a two-level bivariate meta-analysis following a random effects model to summarise the data and fit hierarchical summary receiver-operating characteristic (HSROC) curves. The area under the HSROC curve serves as an indicator of the diagnostic test strength. We calculated summary sensitivity, specificity and negative predictive value (NPV). We assessed agreement of surveillance interval recommendations based on endoscopic diagnosis compared to pathology. RESULTS: For NBI diagnosis of colorectal polyps, the area under the HSROC curve was 0.92 (95% CI 0.90 to 0.94), based on 28 studies involving 6280 polyps in 4053 patients. The overall sensitivity was 91.0% (95% CI 87.6% to 93.5%) and specificity was 82.6% (95% CI 79.0% to 85.7%). In eight studies (n=2146 polyps) that used high-confidence diagnostic predictions, sensitivity was 93.8% and specificity was 83.3%. The NPVs exceeded 90% when 60% or less of all polyps were neoplastic. Surveillance intervals based on endoscopic diagnosis agreed with those based on pathology in 92.6% of patients (95% CI 87.9% to 96.3%). CONCLUSIONS: NBI diagnosis of colorectal polyps is highly accurate--the area under the HSROC curve exceeds 0.90. High-confidence predictions provide >90% sensitivity and NPV. It shows high potential for real-time endoscopic diagnosis.

Endoscopic appearance of proximal colorectal neoplasms and potential implications for colonoscopy in cancer prevention.

BACKGROUND: In everyday practice, the use of colonoscopy for the prevention of colorectal cancer (CRC) is less effective in the proximal than the distal colon. A potential explanation for this is that proximal neoplasms have a more subtle endoscopic appearance, making them more likely to be overlooked. OBJECTIVE: To investigate the differences in endoscopic appearance, ie, diminutive size and nonpolypoid shape, of proximal compared with distal colorectal neoplasms. DESIGN: Cross-sectional, single-center study. SETTING: Endoscopists at the Maastricht University Medical Center in the Netherlands who were previously trained in the detection and classification of nonpolypoid colorectal lesions. PATIENTS: Consecutive patients undergoing elective colonoscopy. MAIN OUTCOME MEASUREMENTS: Endoscopic appearance, ie, diminutive size (<6 mm) or nonpolypoid shape (height less than half of the diameter) of colorectal adenomas and serrated polyps (SPs), with a focus on adenomas with advanced histology, ie, high-grade dysplasia or early CRC and SPs with dysplasia or large size. RESULTS: We included 3720 consecutive patients with 2106 adenomas and 941 SPs. We found that in both men and women, proximal adenomas with high-grade dysplasia/early CRC (n = 181) were more likely to be diminutive or nonpolypoid than distal ones (76.3% vs 26.2%; odds ratio [OR] 9.24; 95% CI, 4.45-19.2; P < .001). Of the proximal adenomas, 84.4% were diminutive or nonpolypoid compared with 68.0% of the distal ones (OR 2.66; 95% CI, 2.14-3.29; P < .001). Likewise, large/dysplastic SPs in the proximal colon were more often nonpolypoid than distal ones (66.2% vs 27.8%; OR 5.51; 95% CI, 2.79-10.9; P < .001). LIMITATIONS: Inclusion of both symptomatic and asymptomatic patients. CONCLUSIONS: Proximal colorectal neoplasms with advanced histology frequently are small or have a nonpolypoid appearance. These findings support careful inspection of the proximal colon, if quality of cancer prevention with the use of colonoscopy is to be optimized.

A tandem colonoscopy study of adenoma miss rates during endoscopic training: a venture into uncharted territory.

BACKGROUND: Tandem colonoscopy is regarded as the reference standard for the evaluation of the adenoma detection rate (ADR) and adenoma miss rate (AMR) during colonoscopy. Pooled results from previous tandem studies yield AMRs of 22%. The AMR of trainees is important to estimate the number of colonoscopies required to develop competence in screening for colorectal neoplasms. OBJECTIVE: To measure the ADR and AMR of trainees as a function of experience. METHODS: Prospective tandem colonoscopy study at an academic VA medical center. A trainee initially attempted colonoscopy. If the trainee was able to intubate the cecum, the trainee performed the withdrawal, and the colonoscopy was then repeated by the attending physician to assess the AMR. RESULTS: Twelve trainee endoscopists were included in the study. Trainees had between 0 and 33 months of previous endoscopic experience and had done between 0 and 605 previous colonoscopies. A total of 230 patients were evaluated for the study, and 218 patients were enrolled. Complete tandem colonoscopy was performed in 147 patients. There was a 54% ADR. The mean (standard deviation) size of the adenomas in the cohort was 5.9 (5.3) mm. Significant variables in multivariate logistic regression analysis for missed adenomas were trainee experience (P = .011) and patient age (P < .001). The AMR decreased with increasing experience, and it is estimated that 450 colonoscopies are required to attain AMRs of less than 25% in a 60-year-old patient. LIMITATIONS: Single-center study; the attending physician performing the second pass was not blinded to the first pass. The AMR was only analyzed for cases in which the trainee was able to reach the cecum with no or minimal assistance. CONCLUSIONS: Our tandem colonoscopy study demonstrates that the AMR decreases as the experience of trainees increases and is a late competency attained during training. Future training may need to incorporate these findings to serve as a basis for determining appropriate training guidelines.

Nonpolypoid colorectal neoplasms: gender differences in prevalence and malignant potential.

OBJECTIVE: Colonoscopy may fail to prevent colorectal cancer, especially in the proximal colon and in women. Nonpolypoid colorectal neoplasms may potentially explain some of these post-colonoscopy cancers. In the present study, we aimed to examine the prevalence and malignant potential of nonpolypoid colorectal neoplasms in a large population, with special attention to gender and location. METHODS: We performed a cross-sectional study of all consecutive patients undergoing elective colonoscopy at a single academic medical center. The endoscopists were familiarized on the detection and treatment of nonpolypoid lesions. Advanced histology was defined by the presence of high-grade dysplasia or early cancer. RESULTS: We included 2310 patients (53.9% women, mean age 58.4 years) with 2143 colorectal polyps. Prevalences of colorectal neoplasms and nonpolypoid colorectal neoplasms were lower in women than in men (20.9% vs. 33.7%, p < 0.001 and 3.0% vs. 5.5%, p = 0.002). In women, nonpolypoid colorectal neoplasms were significantly more likely to contain advanced histology than polypoid ones (OR 2.89, 95% CI 1.24-6.74, p = 0.01), while this was not the case in men (OR 0.91, 95% CI 0.40-2.06, p = 0.83). Proximal neoplasms with advanced histology were more likely to be nonpolypoid than distal ones (OR 4.68, 95% CI 1.54-14.2, p = 0.006). CONCLUSION: Nonpolypoid mechanisms may play an important role in colorectal carcinogenesis, in both women and men. Although women have fewer colorectal neoplasms than men, they have nonpolypoid colorectal neoplasms, which frequently contain advanced histology.

Histologic and molecular analyses of colonic perineurial-like proliferations in serrated polyps: perineurial-like stromal proliferations are seen in sessile serrated adenomas.

Colonic perineuriomas are recently described benign mucosal polyps that are composed of a bland spindle cell proliferation surrounding crypts that often demonstrate hyperplastic/serrated epithelial changes. However, the origin of this unique stromal proliferation is still unclear, and the association with serrated polyps, including sessile serrated adenomas, has not been fully described. We evaluated the pathologic and molecular features of colonic polyps associated with perineurial-like proliferations in 2 retrospective cohorts: (1) a series of 198 consecutive sessile serrated adenomas and (2) 20 colonic polyps diagnosed as a perineurioma irrespective of the presence of serrated colonic crypts. Thirteen of 198 (6.5%) sessile serrated adenomas demonstrated a perineurial-like stromal proliferation, with most (12 of 13, 92%) involving the right (9 cases) and transverse colon (3 cases). In all 13 cases, the perineurial-like proliferation surrounded serrated colonic crypts and typically involved only a small area of the sessile serrated adenoma (average 9% of polyp size; range, 2% to 19%). All 11 polyps evaluated for epithelial membrane antigen (EMA) expression demonstrated stromal EMA staining limited to the perineurial-like proliferation. Twelve of 13 (92%) sessile serrated adenomas with perineurial-like proliferations demonstrated a pV600E BRAF mutation. Of the 20 colonic polyps diagnosed as a perineurioma, 18 (90%) demonstrated serrated crypts intimately associated with the perineurial-like proliferation. In 13 of 18 polyps with associated serrated crypts, all serrated crypts were invested with the perineurial proliferation. In 5 cases, serrated crypts were seen away from the perineurial proliferation. Of these 18 polyps, the majority (16 of 18, 89%) were microvesicular hyperplastic polyps involving the left colon. However, 2 (11%) polyps in the right colon demonstrated histologic features diagnostic of sessile serrated adenoma. All 18 polyps with serrated crypts demonstrated a pV600E BRAF mutation. In contrast, the 2 polyps not associated with serrated crypts were negative for a BRAF mutation. Our results show for the first time that perineurial-like stromal proliferations frequently occur in sessile serrated adenomas. The presence of focal perineurial-like stromal proliferations in sessile serrated adenomas and the common finding of serrated crypts in colonic perineuriomas are likely indicative of an epithelial-stromal interaction, possibly related to some factor elaborated by the serrated epithelium.

Use of an endoscope-compatible probe to detect colonic dysplasia with Fourier transform infrared spectroscopy.

Fourier transform infrared (FTIR) spectroscopy is sensitive to the molecular composition of tissue and has the potential to identify premalignant tissue (dysplasia) as an adjunct to endoscopy. We demonstrate collection of mid-infrared absorption spectra with a silver halide (AgCl(0.4)Br(0.6)) optical fiber and use spectral preprocessing to identify optimal subranges that classify colonic mucosa as normal, hyperplasia, or dysplasia. We collected spectra (n=83) in the 950 to 1800 cm(-1) regime on biopsy specimens obtained from human subjects (n=37). Subtle differences in the magnitude of the absorbance peaks at specific wave numbers were observed. The best double binary algorithm for distinguishing normal-versus-dysplasia and hyperplasia-versus-dysplasia was determined from an exhaustive search of spectral intervals and preprocessing techniques. Partial least squares discriminant analysis was used to classify the spectra using a leave-one-subject-out cross-validation strategy. The results were compared with histology reviewed independently by two gastrointestinal pathologists. The optimal thresholds identified resulted in an overall sensitivity, specificity, accuracy, and positive predictive value of 96%, 92%, 93%, and 82%, respectively. These results indicated that mid-infrared absorption spectra collected remotely with an optical fiber can be used to identify colonic dysplasia with high accuracy, suggesting that continued development of this technique for the early detection of cancer is promising.

Colonoscopy with Polypectomy in Patients Taking Clopidogrel.

BACKGROUND AND AIMS: To investigate the bleeding risk of colonoscopy with polypectomy in patients taking clopidogrel. METHODS: Retrospective review of patients undergoing colonoscopy with polypectomy without interruption of clopidogrel. Patients with lesions larger than 1cm were generally rescheduled for polypectomy off clopidogrel. Most of the polyps were removed using cold snare technique. Endoscopic clips were routinely applied prophylactically. RESULTS: A total of 125 polypectomies were performed in 60 patients. The average polyp size was 5.4 ± 2.1 mm. One patient (1.7%, CI 0.3-8.9%) developed post-polypectomy bleeding that resolved without treatment. Three patients (5%, CI 1.7-14%) had immediate bleeding during the procedure and all resolved with prompt clip application. CONCLUSIONS: Polypectomy of lesions up to 1cm in size can be performed without interruption of clopidogrel.

Prevalence of nonpolypoid (flat and depressed) colorectal neoplasms in asymptomatic and symptomatic adults.

CONTEXT: Colorectal cancer is the second leading cause of cancer death in the United States. Prevention has focused on the detection and removal of polypoid neoplasms. Data are limited on the significance of nonpolypoid colorectal neoplasms (NP-CRNs). OBJECTIVES: To determine the prevalence of NP-CRNs in a veterans hospital population and to characterize their association with colorectal cancer. DESIGN, SETTING, AND PATIENTS: Cross-sectional study at a veterans hospital in California with 1819 patients undergoing elective colonoscopy from July 2003 to June 2004. MAIN OUTCOME MEASURES: Endoscopic appearance, location, size, histology, and depth of invasion of neoplasms. RESULTS: The overall prevalence of NP-CRNs was 9.35% (95% confidence interval [95% CI], 8.05%-10.78%; n = 170). The prevalence of NP-CRNs in the subpopulations for screening, surveillance, and symptoms was 5.84% (95% CI, 4.13%-8.00%; n = 36), 15.44% (95% CI, 12.76%-18.44%; n = 101), and 6.01% (95% CI, 4.17%-8.34%; n = 33), respectively. The overall prevalence of NP-CRNs with in situ or submucosal invasive carcinoma was 0.82% (95% CI, 0.46%-1.36%; n = 15); in the screening population, the prevalence was 0.32% (95% CI, 0.04%-1.17%; n = 2). Overall, NP-CRNs were more likely to contain carcinoma (odds ratio, 9.78; 95% CI, 3.93-24.4) than polypoid lesions, irrespective of the size. The positive size-adjusted association of NP-CRNs with in situ or submucosal invasive carcinoma was also observed in subpopulations for screening (odds ratio, 2.01; 95% CI, 0.27-15.3) and surveillance (odds ratio, 63.7; 95% CI, 9.41-431). The depressed type had the highest risk (33%). Nonpolypoid colorectal neoplasms containing carcinoma were smaller in diameter as compared with the polypoid ones (mean [SD] diameter, 15.9 [10.2] mm vs 19.2 [9.6] mm, respectively). The procedure times did not change appreciably as compared with historical controls. CONCLUSION: In this group of veteran patients, NP-CRNs were relatively common lesions diagnosed during routine colonoscopy and had a greater association with carcinoma compared with polypoid neoplasms, irrespective of size.

Small caliber overtube-assisted colonoscopy.

AIM: To combine the benefits of a new thin flexible scope with elimination of excessive looping through the use of an overtube. METHODS: Three separate retrospective series. Series 1: 25 consecutive male patients undergoing unsedated colonoscopy using the new device at a Veteran's hospital in the United States. Series 2: 75 male patients undergoing routine colonoscopy using an adult colonoscope, pediatric colonoscope, or the new device. Series 3: 35 patients who had incomplete colonoscopies using standard instruments. RESULTS: Complete colonoscopy was achieved in all 25 patients in the unsedated series with a median cecal intubation time of 6 min and a median maximal pain score of 3 on a 0-10 scale. In the 75 routine cases, there was significantly less pain with the thin scope compared to standard adult and pediatric colonoscopes. Of the 35 patients in the previously incomplete colonoscopy series, 33 were completed with the new system. CONCLUSION: Small caliber overtube-assisted colonoscopy is less painful than colonoscopy with standard adult and pediatric colonoscopes. Male patients could undergo unsedated colonoscopy with the new system with relatively little pain. The new device is also useful for most patients in whom colonoscopy cannot be completed with standard instruments.