Validating the Simplified Endoscopic Mucosal Assessment for Crohn's Disease: A Novel Method for Assessing Disease Activity.

BACKGROUND: To demonstrate treatment efficacy in Crohn's disease (CD), regulatory authorities require that trials include an endoscopic remission/response end point; however, standardized endoscopic assessment of disease activity, such as the Simple Endoscopic Score for Crohn's Disease (SES-CD), is not typically recorded by clinicians in practice or outside of clinical trials. The novel Simplified Endoscopic Mucosal Assessment for Crohn's Disease (SEMA-CD) was developed to be easy to use in routine clinical practice and as a trial end point. We conducted a study to assess and validate the reliability and feasibility of SEMA-CD as a measure of endoscopic disease activity. METHODS: Pre- and post-treatment ileocolonoscopy videos of pediatric (n = 36) and adult (n = 74) CD patients from 2 ustekinumab clinical trials were each scored with SEMA-CD by 2 to 3 professional central readers, blinded to clinical history and other video scorings; the correlation between SEMA-CD and SES-CD previously completed during the trials was assessed. Sensitivity to change, inter- and intrarater reliability, and comparative ease of scoring were also assessed. RESULTS: The SEMA-CD strongly correlated with SES-CD (Spearman ρ = 0.89; 95% confidence interval, 0.86-0.92). Pre- to post-treatment changes in SEMA-CD vs in SES-CD were strongly correlated, and the correlation remained strong between the scores when compared by study population (pediatric, adult), disease severity, and video quality. Intra- and inter-rater reliability were good, and SEMA-CD was rated easier than SES-CD to score 63.0% of the time, although slightly more difficult than SES-CD to score <1.0% of the time. CONCLUSIONS: The SEMA-CD is reliable, reproducible, sensitive to change, and easy to use in both pediatric and adult patients with CD.

The clinical significance of serrated polyps.

Colorectal cancer (CRC) is a heterogeneous disorder than arises via multiple distinct pathways, such as the serrated pathway, in which serrated polyps (including variants of hyperplastic polyps) are the precursor lesions. Approximately 15-20% of all CRCs arise via the serrated pathway, and these serrated carcinomas are clinically, morphologically, and molecularly distinct from conventional CRCs. The prevention of serrated carcinomas represents an important clinical challenge. Gastroenterologists need to recognize and remove potential precursor lesions and implement a post-polypectomy surveillance program when appropriate. This article focuses on the characteristics and significance of clinically relevant serrated polyps and addresses implications for CRC prevention practices.

Impact of COVID-19 on Endoscopy Training: Perspectives from a Global Survey of Program Directors and Endoscopy Trainers.

BACKGROUND/AIMS: The coronavirus disease of 2019 (COVID-19) pandemic has impacted the training of medical trainees internationally. The aim of this study was to assess the global impact of COVID-19 on endoscopy training from the perspective of endoscopy trainers and to identify strategies implemented to mitigate the impact on trainee education. METHODS: Teaching faculty of gastroenterology (GI) training programs globally were invited to complete a 36-question web-based survey to report the characteristics of their training programs and the impact of COVID-19 on various aspects of endoscopy training, including what factors decisions were based on. RESULTS: The survey response rate was 52.6% (305 out of 580 individuals); 92.8% reported a negative impact on endoscopy training, with suspension of elective procedures (77.1%) being the most detrimental factor. Geographic variations were noted, with European programs reporting the lowest percentage of trainee participation in procedures. A higher proportion of trainees in the Americas were allowed to continue performing procedures, and trainers from the Americas reported receiving the greatest support for endoscopy teaching. CONCLUSION: This study demonstrated that the COVID-19 pandemic has had a significant negative impact on GI endoscopy training internationally, as reported by endoscopy trainers. Focus-optimizing endoscopy training and assessment of competencies are necessary to ensure adequate endoscopy training.

Variation in the detection of serrated polyps in an average risk colorectal cancer screening cohort.

OBJECTIVES: Serrated polyps are precursors in an alternative pathway to colon cancer. These polyps are frequently sessile or flat, located in the proximal colon, and may be overlooked during colonoscopy. Histological criteria to classify these polyps have only recently been described. This study assessed the variation of serrated polyp detection among endoscopists and pathologists in an average risk-screening cohort and trends in detection over time. METHODS: Endoscopy and pathology reports were reviewed from all average risk-screening colonoscopies at an urban academic medical center from 2006 through 2008. Polyps were classified as adenoma (tubular, tubulovillous, or villous), serrated polyp (hyperplastic polyp (HP), sessile serrated adenoma (SSA), or dysplastic serrated polyp (DSP)), adenocarcinoma, or other. Differences in polyp detection among endoscopists and pathologists were tested with χ(2)-tests. Potential predictors of polyp detection were modeled with Poisson regression. RESULTS: Included in the study were 4,335 polyps from 7,192 colonoscopies. Detection prevalence (patients with at least one polyp per 100 colonoscopies) was 22.2 for adenomas, 11.7 for HP, 0.6 for SSA, and 0.2 for DSP. Detection prevalence of proximal SSAs increased from 0.2 in 2006 to 4.4 in 2008 (P<0.001). Detection prevalences among endoscopists differed significantly for adenomas, HP, and SSA. Classification rates among pathologists differed significantly for HP and SSA, but not for adenoma or DSP. On multivariate analysis, endoscopist was a significant predictor of adenoma, HP, and SSA. Pathologist was a significant predictor of HP, SSA, and DSP, but not adenoma. CONCLUSIONS: This study describes the detection of colorectal polyps in an average risk-screening cohort at an urban academic medical center. Detection of proximal SSAs increased during the study period. Detection of adenoma, HP, and SSA differed significantly by endoscopist. Classification of HP and SSA differed significantly by pathologist. Endoscopy and pathology practices should consider educational interventions to improve serrated polyp detection and standardize classification.

A randomized trial comparing uncovered and partially covered self-expandable metal stents in the palliation of distal malignant biliary obstruction.

BACKGROUND: The most common complication of uncovered biliary self-expandable metal stents (SEMSs) is tumor ingrowth. The addition of an impenetrable covering may prolong stent patency. OBJECTIVE: To compare stent patency between uncovered and partially covered SEMSs in malignant biliary obstruction. DESIGN: Multicenter randomized trial. SETTING: Four teaching hospitals. PATIENTS: Adults with inoperable distal malignant biliary obstruction. INTERVENTIONS: Uncovered or partially covered SEMS insertion. MAIN OUTCOME MEASURES: Time to recurrent biliary obstruction, patient survival, serious adverse events, and mechanism of recurrent biliary obstruction. RESULTS: From October 2002 to May 2008, 129 patients were randomized. Recurrent biliary obstruction was observed in 11 of 61 uncovered SEMSs (18%) and 20 of 68 partially covered SEMSs (29%). The median times to recurrent biliary obstruction were 711 days and 357 days for the uncovered and partially covered SEMS groups, respectively (P = .530). Median patient survival was 239 days for the uncovered SEMS and 227 days for the partially covered SEMS groups (P = .997). Serious adverse events occurred in 27 (44%) and 42 (62%) patients in the uncovered and partially covered SEMS groups, respectively (P = .046). None of the uncovered and 8 (12%) of the partially covered SEMSs migrated (P = .0061). LIMITATIONS: Intended sample size was not reached. Allocation to treatment groups was unequal. CONCLUSIONS: There was no significant difference in time to recurrent biliary obstruction or patient survival between the partially covered and uncovered SEMS groups. Partially covered SEMSs were associated with more serious adverse events, particularly migration.

Comparison of microsatellite instability, CpG island methylation phenotype, BRAF and KRAS status in serrated polyps and traditional adenomas indicates separate pathways to distinct colorectal carcinoma end points.

The aim of this study was to compare BRAF and KRAS, CpG island methylator phenotype (CIMP), and microsatellite instability (MSI) status in each of the histologic categories, including end-point carcinomas with residual adenoma, of the serrated polyp neoplasia pathway and the traditional (nonserrated) adenoma-carcinoma sequence. Deoxyribonucleic acid (DNA) was extracted from the selected samples and assayed for BRAF, KRAS2 codon12, 13, CIMP using markers hMLH1, MGMT, MINT1, MINT2, p16, and MSI using an assay for BAT25 and BAT26. A BRAF mutation was present in 82% of serrated carcinomas (SCas), 62% of serrated adenomas (SAs), 83% of serrated polyps with abnormal proliferation (SPAPs-syn. sessile serrated adenoma [SSA]), 76% of microvesicular serrated polyps (MVSPs), and was not found in any of the histologic categories of the traditional adenoma-carcinoma sequence. KRAS2 mutations were found in 43% of the goblet cell serrated polyp (GCSP) category, 13% of MVSPs, 7% of SPAPs, and 24% of SAs; in 26% of large traditional adenoma (lTAs) compared with small traditional adenomas (sTAs) (0/30; P<0.005) and in 37.3% of traditional carcinomas (TCa). CIMP-H (>1 marker positive) was significantly more frequent in SPAP, SA, and SCa compared with MVSP (P<0.05); CIMP-H was present in 10% of sTAs but was found more frequently in lTA (44.4%; OR 7.2; P=0.007) and TCa (38.9%; OR 5.8; P=0.007). Higher CIMP levels (4 or more markers positive) were significantly more frequent in advanced categories of the serrated pathway (SAs [31%] and SCas [30%]) compared with lTAs [0%] and TCAs [3.4%] (OR 12.2; P=0.02). MSI-H was identified only in the adenocarcinoma component of SCas (9/11) or in the contiguous SAs (3/7). The findings indicate that a BRAF mutation is a specific marker for a serrated polyp pathway that has its origin in a hyperplastic polyp (MVSP) and a potential end point as MSI carcinoma. CIMP-High (CIMP-H) develops early in this sequence and MSI-H develops late. The data provided a less complete picture of a second serrated pathway, identified by a KRAS2 mutation in SAs, but showed that the progressive stages of both iterations of the serrated neoplasia pathway are separate and distinct from those of the traditional adenoma-carcinoma sequence.

Central endoscopy reads in inflammatory bowel disease clinical trials: The role of the imaging core lab.

Clinical trials in inflammatory bowel disease (IBD) are evolving at a rapid pace by employing central reading for endoscopic mucosal assessment in a field that was, historically, largely based on assessments by local physicians. This transition from local to central reading carries with it numerous technical, operational, and scientific challenges, many of which can be resolved by imaging core laboratories (ICLs), a concept that has a longer history in clinical trials in a number of diseases outside the realm of gastroenterology. For IBD trials, ICLs have the dual goals of providing objective, consistent assessments of endoscopic findings using central-reading paradigms whilst providing important expertise with regard to operational issues and regulatory expectations. This review focuses on current approaches to using ICLs for central endoscopic reading in IBD trials.

Elastic scattering spectroscopy as an optical marker of inflammatory bowel disease activity and subtypes.

BACKGROUND: In 10% to 15% of individuals, inflammatory bowel disease (IBD) is difficult to classify as ulcerative colitis (UC) or Crohn's disease (CD). Previous work has demonstrated that probe-based elastic scattering spectroscopy (ESS) can produce spectra, informed by parameters like tissue ultrastructure and hemoglobin content, capable of differentiating pathologies. This study investigates whether ESS is an in vivo optical biomarker for the presence, activity, and type of IBD in the colon. METHODS: Pilot study, a retrospective data analysis. ESS spectra of endoscopically normal and inflamed colon were obtained from 48 patients with IBD and 46 non-IBD controls. Measurements from patients with IBD were categorized as CD or UC based on clinical diagnosis. Spectra were analyzed using high-dimensional methods. Leave-one-patient-out cross-validation was used to obtain diagnostic performance estimates. RESULTS: Patients with IBD were distinguishable from non-IBD controls with a sensitivity of 0.93 and specificity of 0.91 based on readings from endoscopically normal mucosa, and 0.94 and 0.93 from inflamed mucosa. In patients with IBD, histologically normal and inflamed colon were distinguishable with per-class accuracies of 0.83 and 0.89, respectively; histologically normal from inactive inflammation with accuracies of 0.73 and 0.89, respectively; and inactive from active colitis with accuracies of 0.87 and 0.84, respectively. The diagnosis of CD versus UC was made with per-class accuracies of 0.92 and 0.87 in normal and 0.87 and 0.85 in inflamed mucosa, respectively. CONCLUSIONS: ESS, a simple, low-cost clinically friendly optical biopsy modality, has the potential to enhance the endoscopic assessment of IBD and its activity in real time and may help to distinguish CD from UC.

Endoscopy in the bariatric surgical patient.

Endoscopy in the bariatric surgical patient presents a new challenge for gastroenterologists, one that will be encountered with increasing frequency as the performance of bariatric surgery increases. To ensure a safe, successful, and useful endoscopy, it is important to be familiar with the expected postsurgical anatomy and endoscopic appearance after the various bariatric operations and common complications that can arise.

Treatment of Biliary Problems in Inflammatory Bowel Disease.

The most common biliary problem in patients with inflammatory bowel disease is primary sclerosing cholangitis (PSC). The treatment of this disease is multifaceted and frequently requires a multidisciplinary approach involving internists, nutritionists, gastroenterologists, and surgeons. Unfortunately, other than liver transplantation, no therapy that is currently available has been proven to alter the natural history of PSC or prolong survival. Ursodeoxycholic acid is currently the most promising pharmacologic treatment option for slowing disease progression and should be used in higher than usual doses (20 to 30 mg/kg/d). Treatment of symptoms due to cholestasis, such as pruritis and steatorrhea, is an important aspect of the medical care of patients with PSC. Our preferred treatment of pruritis due to cholestasis is with bile acid binding exchange resins such as cholestyramine or colestipol (which is generally better tolerated than cholestyramine). Endoscopic therapy should be reserved for patients with obstructive jaundice, cholangitis, or symptomatic dominant biliary strictures. We recommend dilation of dominant strictures with graduated or balloon dilators followed by temporary stenting if the postdilation cholangiographic appearance is not improved or adequate biliary drainage cannot be assured. There is indirect evidence that the combination of ursodeoxycholic acid and endoscopic therapy to maintain biliary patency may improve transplant-free survival in patients with PSC, although this remains to be proven. Liver transplantation remains the only effective treatment of advanced PSC, and should be considered in patients with complications of cirrhosis or intractable pruritis or fatigue.

Colorectal cancer screening in average risk individuals.

Colorectal cancer is the third leading type of cancer, and the second leading cause of cancer-related death in the United States. Prevention of colorectal cancer should be achievable by screening programs that detect adenomas in asymptomatic patients and lead to their removal. In this manuscript, we review the major screening modalities, the advantages and disadvantages of each approach, the data supporting their use, and various issues affecting the implementation of each test. Screening guidelines will be reviewed, and future techniques for colorectal cancer screening examined.

Nonvariceal upper gastrointestinal bleeding.

Nonvariceal UGI bleeding is one of the most common emergencies that gastroenterologists encounter, and continues to be a significant cause of morbidity and mortality. The keys to management are rapid resuscitation and stabilization; appropriate triage based on pre-endoscopic risk factors; early endoscopy to achieve prompt diagnosis and implement hemostatic therapy to high-risk lesions; and aggressive antisecretory therapy (in the case of peptic ulcer bleeding) to reduce the risk of continued or recurrent bleeding.

Endoscopic findings and their clinical correlations in patients with symptoms after gastric bypass surgery.

BACKGROUND: The aim of this study was to describe the endoscopic findings in patients with upper GI symptoms after Roux-en-Y gastric bypass surgery and to correlate clinical features with endoscopic findings. METHODS: Patients with symptoms after Roux-en-Y gastric bypass referred for endoscopy were studied. Endoscopy was performed in standard fashion with a 9.8-mm diameter endoscope. RESULTS: Forty-nine patients underwent a total of 69 upper endoscopy procedures between January 2001 and February 2003. The most common endoscopic findings were the following: normal post-surgical anatomy (21 patients, 43%), marginal ulcer (13 patients, 27%), stomal stenosis (9 patients [19%], including 5 with a concomitant marginal ulcer), and staple-line dehiscence (8 patients [16%], including one with a marginal ulcer). Abdominal pain was the most common symptom (26 patients, 53%) and was more frequent among patients with a normal endoscopy compared with those with an abnormal endoscopy (p=0.04). Stomal stenosis was present in 39% of patients with nausea, vomiting, or dysphagia; it was not present in any patient without these symptoms (p=0.001). Fifteen percent of procedures performed within the first 6 postoperative months were normal, compared with 53% of those performed beyond 6 months (p=0.02). There was no complication of endoscopy. CONCLUSIONS: Among patients with symptoms after Roux-en-Y gastric bypass presenting for endoscopy, normal post-surgical anatomy was the most common finding. Marginal ulcer was the most common abnormality. Presentation with abdominal pain and performance of endoscopy beyond the 6th post-operative month were predictive of a normal endoscopy, and lack of nausea, vomiting, and dysphagia predicted the absence of stomal stenosis.