The Non-Invasive Prediction of Colorectal Neoplasia (NIPCON) Study 1995-2022: A Comparison of Guaiac-Based Fecal Occult Blood Test (FOBT) and an Anti-Adenoma Antibody, Adnab-9.

Given the need to improve the sensitivity of non-invasive methods to detect colorectal neoplasia, particularly adenomas, we compared a fecal test using a monoclonal antibody (Mab) raised against constituents of colonic adenomas designated Adnab-9 (Adenoma Antibody 9), recognizing an N-linked 87 kDa glycoprotein, to gFOBT, which is shown to reduce CRC mortality. p87 immunohistochemistry testing is significantly more sensitive (OR 3.64[CI 2.37-5.58]) than gFOBT (guaiac-based fecal occult blood test) for adenomas (<3 in number), advanced adenomas (OR 4.21[CI 2.47-7.15]), or a combination of the two (OR 3.35[CI 2.47-4.53]). p87 immunohistochemistry shows regional Paneth cell (PC) expression mainly in the right-sided colon and is significantly reduced in the ceca of African Americans (p < 0.0001). In a subset of patients, we obtained other body fluids such as urine, colonic effluent, and saliva. Urine tests (organ-specific neoantigen) showed a significant difference for advanced adenomas (p < 0.047). We conclude that fecal p87 testing is more sensitive than gFOBT and Adnab-9 and could be used to better direct the colonoscopy screening effort.

Cold versus hot snare resection with or without submucosal injection of 6- to 15-mm colorectal polyps: a randomized controlled trial.

BACKGROUND AND AIMS: Cold snare resection of colorectal lesions has been found to be safe and effective for an expanding set of colorectal lesions. In this study, we sought to understand the efficacy of simple cold snare resection and cold EMR versus hot snare resection and hot EMR for colorectal lesions 6 to 15 mm in size. METHODS: At 3 U.S. centers, 235 patients with 286 colorectal lesions 6 to 15 mm in size were randomized to cold snaring, cold EMR, hot snaring, or hot EMR for nonpedunculated colorectal lesions 6 to 15 mm in size. The primary outcome was complete resection determined by 4 biopsy samples from the defect margin and 1 biopsy sample from the center of the resection defect. RESULTS: The overall incomplete resection rate was 2.4% (95% confidence interval [CI], .8%-7.5%). All 7 incompletely removed polyps were 10 to 15 mm in size and removed by hot EMR (n = 4, 6.2%), hot snare (n = 2, 2.2%), or cold EMR (n = 1, 1.8%). Cold snaring had no incomplete resections, required less procedural time than the other methods, and was not associated with serious adverse events. CONCLUSIONS: Cold snaring is a dominant resection technique for nonpedunculated colorectal lesions 6 to 15 mm in size. (Clinical trial registration number: NCT03462706.).

Effects of Blended (Yellow) vs Forced Coagulation (Blue) Currents on Adverse Events, Complete Resection, or Polyp Recurrence After Polypectomy in a Large Randomized Trial.

BACKGROUND & AIMS: There is debate over the type of electrosurgical setting that should be used for polyp resection. Some endoscopists use a type of blended current (yellow), whereas others prefer coagulation (blue). We performed a single-blinded, randomized trial to determine whether type of electrosurgical setting affects risk of adverse events or recurrence. METHODS: Patients undergoing endoscopic mucosal resection of nonpedunculated colorectal polyps 20 mm or larger (n = 928) were randomly assigned, in a 2 × 2 design, to groups that received clip closure or no clip closure of the resection defect (primary intervention) and then to either a blended current (Endocut Q) or coagulation current (forced coagulation) (Erbe Inc) (secondary intervention and focus of the study). The study was performed at multiple centers, from April 2013 through October 2017. Patients were evaluated 30 days after the procedure (n = 919), and 675 patients underwent a surveillance colonoscopy at a median of 6 months after the procedure. The primary outcome was any severe adverse event in a per patient analysis. Secondary outcomes were complete resection and recurrence at first surveillance colonoscopy in a per polyp analysis. RESULTS: Serious adverse events occurred in 7.2% of patients in the Endocut group and 7.9% of patients in the forced coagulation group, with no significant differences in the occurrence of types of events. There were no significant differences between groups in proportions of polyps that were completely removed (96% in the Endocut group vs 95% in the forced coagulation group) or the proportion of polyps found to have recurred at surveillance colonoscopy (17% and 17%, respectively). Procedural characteristics were comparable, except that 17% of patients in the Endocut group had immediate bleeding that required an intervention, compared with 11% in the forced coagulation group (P = .006). CONCLUSIONS: In a randomized trial to compare 2 commonly used electrosurgical settings for the resection of large colorectal polyps (Endocut vs forced coagulation), we found no difference in risk of serious adverse events, complete resection rate, or polyp recurrence. Electrosurgical settings can therefore be selected based on endoscopist expertise and preference. Clinicaltrials.gov ID NCT01936948.

Factors associated with complete clip closure after endoscopic mucosal resection of large colorectal polyps.

BACKGROUND AND STUDY AIM : Delayed bleeding is a common adverse event following endoscopic mucosal resection (EMR) of large colorectal polyps. Prophylactic clip closure of the mucosal defect after EMR of nonpedunculated polyps larger than 20 mm reduces the incidence of severe delayed bleeding, especially in proximal polyps. This study aimed to evaluate factors associated with complete prophylactic clip closure of the mucosal defect after EMR of large polyps. METHODS : This is a post hoc analysis of the CLIP study (NCT01936948). All patients randomized to the clip group were included. Main outcome was complete clip closure of the mucosal resection defect. The defect was considered completely closed when no remaining mucosal defect was visible and clips were less than 1 cm apart. Factors associated with complete closure were evaluated in multivariable analysis. RESULTS : In total, 458 patients (age 65, 58 % men) with 494 large polyps were included. Complete clip closure of the resection defect was achieved for 338 polyps (68.4 %); closure was not complete for 156 (31.6 %). Factors associated with complete closure in adjusted analysis were smaller polyp size (odds ratio 1.06 for every millimeter decrease [95 % confidence interval 1.02-1.08]), good access (OR 3.58 [1.94-9.59]), complete submucosal lifting (OR 2.28 [1.36-3.90]), en bloc resection (OR 5.75 [1.48-22.39]), and serrated histology (OR 2.74 [1.35-5.56]). CONCLUSIONS : Complete clip closure was not achieved for almost one in three resected large nonpedunculated polyps. While stable access and en bloc resection facilitate clip closure, most factors associated with clip closure are not modifiable. This highlights the need for alternative closure options and measures to prevent bleeding.

Prevalence of Advanced Colorectal Neoplasia in Veterans: Effects of Age, Sex, and Race/Ethnicity.

GOAL: We sought to quantify the independent effects of age, sex, and race/ethnicity on risk of colorectal cancer (CRC) and advanced neoplasia (AN) in Veterans. STUDY: We conducted a retrospective, cross-sectional study of Veterans aged 40 to 80 years who had diagnostic or screening colonoscopy between 2002 and 2009 from 1 of 14 Veterans Affairs Medical Centers. Natural language processing identified the most advanced finding and location (proximal, distal). Logistic regression was used to examine the adjusted, independent effects of age, sex, and race, both overall and in screening and diagnostic subgroups. RESULTS: Among 90,598 Veterans [mean (SD) age 61.7 (9.4) y, 5.2% (n=4673) were women], CRC and AN prevalence was 1.3% (n=1171) and 8.9% (n=8081), respectively. Adjusted CRC risk was higher for diagnostic versus screening colonoscopy [odds ratio (OR)=3.79; 95% confidence interval (CI), 3.19-4.50], increased with age, was numerically (but not statistically) higher for men overall (OR=1.53; 95% CI, 0.97-2.39) and in the screening subgroup (OR=2.24; 95% CI, 0.71-7.05), and was higher overall for Blacks and Hispanics, but not in screening. AN prevalence increased with age, and was present in 9.2% of men and 3.9% of women [adjusted OR=1.90; 95% CI, 1.60-2.25]. AN risk was 11% higher in Blacks than in Whites overall (OR=1.11; 95% CI, 1.04-1.20), was no different in screening, and was lower in Hispanics (OR=0.74; 95% CI, 0.55-0.98). Women had more proximal CRC (63% vs. 39% for men; P=0.03), but there was no difference in proximal AN (38.3% for both genders). CONCLUSIONS: Age and race were associated with AN and CRC prevalence. Blacks had a higher overall prevalence of both CRC and AN, but not among screenings. Men had increased risk for AN, while women had a higher proportion of proximal CRC. These findings may be used to tailor when and how Veterans are screened for CRC.

Clip Closure Prevents Bleeding After Endoscopic Resection of Large Colon Polyps in a Randomized Trial.

BACKGROUND & AIMS: Bleeding is the most common severe complication after endoscopic mucosal resection of large colon polyps and is associated with significant morbidity and cost. We examined whether prophylactic closure of the mucosal defect with hemoclips after polyp resection reduces the risk of bleeding. METHODS: We performed a multicenter, randomized trial of patients with a large nonpedunculated colon polyp (≥20 mm) at 18 medical centers in North America and Spain from April 2013 through October 2017. Patients were randomly assigned to groups that underwent endoscopic closure with a clip (clip group) or no closure (control group) and followed. The primary outcome, postprocedure bleeding, was defined as a severe bleeding event that required hospitalization, a blood transfusion, colonoscopy, surgery, or another invasive intervention within 30 days after completion of the colonoscopy. Subgroup analyses included postprocedure bleeding with polyp location, polyp size, or use of periprocedural antithrombotic medications. We also examined the risk of any serious adverse event. RESULTS: A total of 919 patients were randomly assigned to groups and completed follow-up. Postprocedure bleeding occurred in 3.5% of patients in the clip group and 7.1% in the control group (absolute risk difference [ARD] 3.6%; 95% confidence interval [CI] 0.7%-6.5%). Among 615 patients (66.9%) with a proximal large polyp, the risk of bleeding in the clip group was 3.3% and in the control group was 9.6% (ARD 6.3%; 95% CI 2.5%-10.1%); among patients with a distal large polyp, the risks were 4.0% in the clip group and 1.4% in the control group (ARD -2.6%; 95% CI -6.3% to -1.1%). The effect of clip closure was independent of antithrombotic medications or polyp size. Serious adverse events occurred in 4.8% of patients in the clip group and 9.5% of patients in the control group (ARD 4.6%; 95% CI 1.3%-8.0%). CONCLUSIONS: In a randomized trial, we found that endoscopic clip closure of the mucosal defect following resection of large colon polyps reduces risk of postprocedure bleeding. The protective effect appeared to be restricted to large polyps located in the proximal colon. ClinicalTrials.gov no: NCT01936948.

The Association Between Nonalcoholic Fatty Liver Disease and Metabolic Abnormalities in The United States Population.

BACKGROUND: Prevalence of nonalcoholic fatty liver disease (NAFLD) and rate of advanced fibrosis among individuals with metabolic syndrome (MetS) and its individual metabolic abnormalities needs better understanding in the United States population. We aim to study these by using a large United States population database, the Third National Health and Nutrition Examination Survey (NHANES III). METHODS: A total of 11,674 individuals were included in our study cohort. NAFLD was defined as presence of moderate to severe hepatic steatosis on liver ultrasound in absence of viral hepatitis, significant alcohol use, elevated transferrin level, and medication use leading to hepatic steatosis. Advanced fibrosis among those with NAFLD was determined using noninvasive method, the NAFLD fibrosis score. MetS was defined based on the National Cholesterol Education Program Adult Treatment Panel III definition. RESULTS: The prevalence of NAFLD among included study cohort was 18.2% (95% confidence interval, 16.5-19.9). Individuals with metabolic abnormalities demonstrated higher prevalence (MetS, 43.2%; increased waist circumference, 31.2%; impaired fasting glucose/diabetes, 41.2%; high triglyceride level, 34.7%; low high-density lipoprotein, 27.8%; high blood pressure, 29.2%). The individuals with MetS had significantly higher NAFLD prevalence compared with controls (adjusted odds ratio, 11.5; 95% confidence interval, 8.9-14.7). The severity of hepatic steatosis was also noted to increase with higher number of metabolic abnormalities. Among individual metabolic abnormalities, increased waist circumference, impaired fasting glucose/diabetes, high triglyceride, and low high-density lipoprotein levels were found to be independently associated with NAFLD. Individuals with impaired fasting glucose/diabetes and those with 5 metabolic abnormalities had higher rate of advanced fibrosis (18.6% and 30.3%, respectively). Prevalence of NAFLD among individuals without any metabolic abnormality was 6.1%. CONCLUSION: Prevalence of NAFLD and rate of advanced fibrosis are significantly high among individuals with metabolic abnormalities.

Multi-center colonoscopy quality measurement utilizing natural language processing.

BACKGROUND: An accurate system for tracking of colonoscopy quality and surveillance intervals could improve the effectiveness and cost-effectiveness of colorectal cancer (CRC) screening and surveillance. The purpose of this study was to create and test such a system across multiple institutions utilizing natural language processing (NLP). METHODS: From 42,569 colonoscopies with pathology records from 13 centers, we randomly sampled 750 paired reports. We trained (n=250) and tested (n=500) an NLP-based program with 19 measurements that encompass colonoscopy quality measures and surveillance interval determination, using blinded, paired, annotated expert manual review as the reference standard. The remaining 41,819 nonannotated documents were processed through the NLP system without manual review to assess performance consistency. The primary outcome was system accuracy across the 19 measures. RESULTS: A total of 176 (23.5%) documents with 252 (1.8%) discrepant content points resulted from paired annotation. Error rate within the 500 test documents was 31.2% for NLP and 25.4% for the paired annotators (P=0.001). At the content point level within the test set, the error rate was 3.5% for NLP and 1.9% for the paired annotators (P=0.04). When eight vaguely worded documents were removed, 125 of 492 (25.4%) were incorrect by NLP and 104 of 492 (21.1%) by the initial annotator (P=0.07). Rates of pathologic findings calculated from NLP were similar to those calculated by annotation for the majority of measurements. Test set accuracy was 99.6% for CRC, 95% for advanced adenoma, 94.6% for nonadvanced adenoma, 99.8% for advanced sessile serrated polyps, 99.2% for nonadvanced sessile serrated polyps, 96.8% for large hyperplastic polyps, and 96.0% for small hyperplastic polyps. Lesion location showed high accuracy (87.0-99.8%). Accuracy for number of adenomas was 92%. CONCLUSIONS: NLP can accurately report adenoma detection rate and the components for determining guideline-adherent colonoscopy surveillance intervals across multiple sites that utilize different methods for reporting colonoscopy findings.

Past exposure to hepatitis B: a risk factor for increase in mortality?

BACKGROUND: Chronic hepatitis B has been shown to increase mortality, but association of past exposure to hepatitis B and mortality has not been studied well. The aim of this study was to evaluate the risk of overall and liver-related mortality in individuals with past exposure to hepatitis B. METHODS: The National Health and Nutrition Examination Survey III (NHANES III) and its related public linked mortality files were used for this study. The participants with presence of anti-HBc ± anti-HBs, in absence of hepatitis B surface antigen were considered to have previous exposure to hepatitis B. The overall mortality from past exposure to hepatitis B was assessed in participants without any chronic liver diseases (CLD) and in participants with chronic hepatitis C, alcoholic liver disease (ALD), and nonalcoholic fatty liver disease. The Cox proportional regression analysis was used to calculate adjusted hazard ratios. RESULTS: A total of 15,650 individuals were included in the analyses. Past exposure to hepatitis B was an independent predictor of increase in overall mortality in individuals without CLD [adjusted hazard ratio (aHR)=1.29; 95% confidence interval (CI), 1.06-1.56; P=0.012] and those with ALD (aHR=2.25; 95% CI, 1.20-4.23; P=0.013). It was also an independent predictor of liver-related mortality in ALD cohort (aHR=7.75; 95% CI, 2.56-23.48; P<0.001). Past exposure to hepatitis B did not correlate with a significant increase in overall or liver-related mortality in chronic hepatitis C or nonalcoholic fatty liver disease cohorts. CONCLUSION: Past exposure to hepatitis B is associated with significant increase in overall mortality among individuals with ALD and those without CLD.

Acceptance of split-dose bowel preparation regimen for colonoscopy by patients and providers.

BACKGROUND: Split-dose bowel preparation (split prep) for colonoscopy has been shown to be superior to conventional dosing (entire dose taken on the evening preceding colonoscopy) and has been endorsed by recent guidelines. A potential limitation is the requirement for patients to wake up early to drink the second half. METHODS: A group of colonoscopy patients, scheduled for morning procedures were surveyed regarding their opinion about a split prep regimen. The survey specifically asked if they would be willing to wake up at 4:00 AM to drink the second half of the preparation. Primary care providers (PCPs) were given a similar survey asking for their opinion about the willingness of their patients to take a split prep regimen. RESULTS: Among the 149 patients surveyed, 95 patients (64%) were willing to wake up early to complete a split prep, whereas 54 (36%) were not. The majority, 65 of 95 (68%) patients, preferred an early morning appointment. Only 3 of 95 (3%) patients preferred an afternoon one. There were no statistically significant differences between patients in favor of a split or conventional preparation, in respect to demographics, family history of colorectal cancer, or prior experience with colonoscopy. A total of 25 of 34 PCPs (74%) answered the survey. Only 14 PCPs (56%) thought their patients would be willing to wake up at 4:00 AM to complete the preparation. CONCLUSIONS: Despite a high level of apprehension among PCPs, the majority of colonoscopy patients seem willing to comply with a split prep. Therefore, split prep should be used whenever possible for colonoscopy.

Baseline Features and Reasons for Nonparticipation in the Colonoscopy Versus Fecal Immunochemical Test in Reducing Mortality From Colorectal Cancer (CONFIRM) Study, a Colorectal Cancer Screening Trial.

Importance: The Colonoscopy Versus Fecal Immunochemical Test in Reducing Mortality From Colorectal Cancer (CONFIRM) randomized clinical trial sought to recruit 50 000 adults into a study comparing colorectal cancer (CRC) mortality outcomes after randomization to either an annual fecal immunochemical test (FIT) or colonoscopy. Objective: To (1) describe study participant characteristics and (2) examine who declined participation because of a preference for colonoscopy or stool testing (ie, fecal occult blood test [FOBT]/FIT) and assess that preference's association with geographic and temporal factors. Design, Setting, and Participants: This cross-sectional study within CONFIRM, which completed enrollment through 46 Department of Veterans Affairs medical centers between May 22, 2012, and December 1, 2017, with follow-up planned through 2028, comprised veterans aged 50 to 75 years with an average CRC risk and due for screening. Data were analyzed between March 7 and December 5, 2022. Exposure: Case report forms were used to capture enrolled participant data and reasons for declining participation among otherwise eligible individuals. Main Outcomes and Measures: Descriptive statistics were used to characterize the cohort overall and by intervention. Among individuals declining participation, logistic regression was used to compare preference for FOBT/FIT or colonoscopy by recruitment region and year. Results: A total of 50 126 participants were recruited (mean [SD] age, 59.1 [6.9] years; 46 618 [93.0%] male and 3508 [7.0%] female). The cohort was racially and ethnically diverse, with 748 (1.5%) identifying as Asian, 12 021 (24.0%) as Black, 415 (0.8%) as Native American or Alaska Native, 34 629 (69.1%) as White, and 1877 (3.7%) as other race, including multiracial; and 5734 (11.4%) as having Hispanic ethnicity. Of the 11 109 eligible individuals who declined participation (18.0%), 4824 (43.4%) declined due to a stated preference for a specific screening test, with FOBT/FIT being the most preferred method (2820 [58.5%]) vs colonoscopy (1958 [40.6%]; P < .001) or other screening tests (46 [1.0%] P < .001). Preference for FOBT/FIT was strongest in the West (963 of 1472 [65.4%]) and modest elsewhere, ranging from 199 of 371 (53.6%) in the Northeast to 884 of 1543 (57.3%) in the Midwest (P = .001). Adjusting for region, the preference for FOBT/FIT increased by 19% per recruitment year (odds ratio, 1.19; 95% CI, 1.14-1.25). Conclusions and Relevance: In this cross-sectional analysis of veterans choosing nonenrollment in the CONFIRM study, those who declined participation more often preferred FOBT or FIT over colonoscopy. This preference increased over time and was strongest in the western US and may provide insight into trends in CRC screening preferences.

Associations between markers of colorectal cancer stem cells and adenomas among ethnic groups.

BACKGROUND AND PURPOSES: Most colorectal tumors develop from adenomatous polyps, which are detected by colonoscopy. African Americans (AAs) have higher incidence of colorectal cancer (CRC) and greater mortality from this disease than Caucasian Americans (CAs). We investigated whether differences in predisposition to CRC and its surrogate (colonic adenomas) between these ethnic groups were related to numbers of cancer stem or stem-like cells (CSCs) in colonocytes. METHODS: We analyzed colonic effluent from 11 AA and 14 CA patients who underwent scheduled colonoscopy examinations at the John D. Dingell Veterans Affairs Medical Center. We determined proportions of cells that expressed the CSC markers CD44 and CD166 by flow cytometry. RESULTS: The proportion of colonocytes that were CD44(+)CD166(-) in effluent from patients with adenomas was significantly greater than from patients without adenomas (P = 0.01); the proportion of CD44(+)CD166(+) colonocytes was also greater (P = 0.07). Effluent from AAs with adenomas had 60 % more CD44(+)166(-) colonocytes than from CAs with adenomas. Using cutoff values of 8 % for AAs and 3 % for CAs, the proportion of CD44(+)166(-) colonocytes that had positive predictive value for detection of adenomas was 100 % for AAs and CAs, determined by receiver operator characteristic curve analysis. CONCLUSION: The proportion of CD44(+)166(-) colonocytes in colonic effluent can be used to identify patients with adenoma. AAs with adenomas have a higher proportion of CD44(+)166(-) colonocytes than CA. The increased proportion of CSCs in colonic tissue from AA might be associated with the increased incidence of CRC in this population.

Ogilvie syndrome and herpes zoster: case report and review of the literature.

BACKGROUND: The very unusual association between herpes zoster and Ogilvie syndrome has received scant attention in the published literature. OBJECTIVES: This review discusses the published experience since 1950 and attempts to increase clinical awareness about the co-existence of both conditions. CASE REPORT: An 84-year-old male patient affected by herpes zoster presented with advanced acute colonic pseudo-obstruction and was successfully treated with colonic diversion. DISCUSSION: Twenty published studies (1950-2008) of 28 patients in whom the two conditions co-existed are reviewed. The review included 22 male and 7 female patients (24%) aged 32-87 years (mean, 61 years). Significant co-morbidities were present in 45% of the patients. The majority of patients were observed and treated conservatively (83%). Two patients died (7%), both suffering from respiratory complications and malignancy. CONCLUSION: Recognition of the combined syndrome may help to avoid unnecessary surgery. Laparotomy should be reserved as a last resort for when the obstruction cannot be successfully managed by endoscopy. A diverting colostomy can be used to monitor the blood supply and thus provide early warning for an impending abdominal catastrophe.