The Role of Imaging for GI Bleeding: ACG and SAR Consensus Recommendations.

Gastrointestinal (GI) bleeding is the most common GI diagnosis leading to hospitalization within the United States. Prompt diagnosis and treatment of GI bleeding is critical to improving patient outcomes and reducing high health care utilization and costs. Radiologic techniques including CT angiography, catheter angiography, CT enterography, MR enterography, nuclear medicine red blood cell scan, and technetium-99m pertechnetate scintigraphy (Meckel scan) are frequently used to evaluate patients with GI bleeding and are complementary to GI endoscopy. However, multiple management guidelines exist, which differ in the recommended utilization of these radiologic examinations. This variability can lead to confusion as to how these tests should be used in the evaluation of GI bleeding. In this document, a panel of experts from the American College of Gastroenterology and Society of Abdominal Radiology provide a review of the radiologic examinations used to evaluate for GI bleeding including nomenclature, technique, performance, advantages, and limitations. A comparison of advantages and limitations relative to endoscopic examinations is also included. Finally, consensus statements and recommendations on technical parameters and utilization of radiologic techniques for GI bleeding are provided. © Radiological Society of North America and the American College of Gastroenterology, 2024. Supplemental material is available for this article. This article is being published concurrently in American Journal of Gastroenterology and Radiology. The articles are identical except for minor stylistic and spelling differences in keeping with each journal's style. Citations from either journal can be used when citing this article. See also the editorial by Lockhart in this issue.

Phase I double-blind, placebo-controlled trial of dolcanatide (SP-333) 27 mg to explore colorectal bioactivity in healthy volunteers.

Guanylyl cyclase C (GUCY2C) is a tumor-suppressing receptor silenced by loss of expression of the luminocrine hormones guanylin and uroguanylin early in colorectal carcinogenesis. This observation suggests oral replacement with a GUCY2C agonist may be an effective targeted chemoprevention agent. Previous studies revealed that linaclotide, an oral GUCY2C agonist formulated for gastric release, did not persist to activate guanylyl cyclase signaling in the distal rectum. Dolcanatide is an investigational oral uroguanylin analog, substituted with select D amino acids, for enhanced stability and extended persistence to activate GUCY2C in small and large intestine. However, the ability of oral dolcanatide to induce a pharmacodynamic (PD) response by activating GUCY2C in epithelial cells of the colorectum in humans remains undefined. Here, we demonstrate that administration of oral dolcanatide 27 mg daily for 7 d to healthy volunteers did not activate GUCY2C, quantified as accumulation of its product cyclic GMP, in epithelial cells of the distal rectum. These data reveal that the enhanced stability of dolcanatide, with persistence along the rostral-caudal axis of the small and large intestine, is inadequate to regulate GUCY2C across the colorectum to prevent tumorigenesis. These results highlight the importance of developing a GUCY2C agonist for cancer prevention formulated for release and activity targeted to the colorectum.

Multicentre, prospective, randomised study comparing the diagnostic yield of colon capsule endoscopy versus CT colonography in a screening population (the TOPAZ study).

OBJECTIVE: Colon capsule endoscopy (CCE) has shown promise for colorectal neoplasia detection compared with optical colonoscopy (OC), but has not been compared with other screening tests in average risk screening patients. DESIGN: Patients 50 to 75 years of age (African Americans, 45-75 years) were randomised to CCE or CT colonography (CTC) and subsequent blinded OC. The primary endpoint was diagnostic yield of polyps ≥6 mm with CCE or CTC. Secondary endpoints included accuracy for size and histology, examination completeness, number/proportion of subjects with polyps and adenomas ≥6 mm and ≥10 mm, subject satisfaction and safety. RESULTS: From 320 enrolled subjects, data from 286 (89.4%) were evaluable. The proportion of subjects with any polyp ≥6 mm confirmed by OC was 31.6% for CCE versus 8.6% for CTC (pPr non-inferiority and superiority=0.999). The diagnostic yield of polyps ≥10 mm was 13.5% with CCE versus 6.3% with CTC (pPr non-inferiority=0.9954). The sensitivity and specificity of CCE for polyps ≥6 mm was 79.2% and 96.3% while that of CTC was 26.8% and 98.9%. The sensitivity and specificity of CCE for polyps ≥10 mm was 85.7% and 98.2% compared with 50% and 99.1% for CTC. Both tests were well tolerated/safe. CONCLUSION: CCE was superior to CTC for detection of polyps ≥6 mm and non-inferior for identification of polyps ≥10 mm. CCE should be considered comparable or superior to CTC as a colorectal neoplasia screening test, although neither test is as effective as OC. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov no: NCT02754661.

The gut microbiome and colorectal cancer: a review of bacterial pathogenesis.

Colorectal cancer (CRC) is the third most common newly diagnosed cancer in both men and women in the Unites States. Colonoscopy has become increasingly popular in CRC screening and represents the gold standard for detecting and removing pre-cancerous lesions. Although colonoscopy is considered a relatively safe procedure, it is invasive and bowel preparation can be challenging for patients. As interest in the gut microbiome has expanded, there have been new links established between bacteria and the development of CRC. These developing associations could prove to be a useful adjunct to colonoscopy for CRC screening in the future. This review examines current research evaluating multiple proposed pathogenic microorganisms including sulfidogenic bacteria such as Bilophila wadsworthia, as well as Streptococcus bovis, Helicobacter pylori, Bacteroides fragilis, and Clostridium septicum. This discussion primarily focuses on bacterial pathogenesis, evidence of association with CRC, and the proposed mechanisms of carcinogenesis.

Bioactivity of Oral Linaclotide in Human Colorectum for Cancer Chemoprevention.

Guanylate cyclase C (GUCY2C) is a tumor-suppressing receptor silenced by loss of expression of its luminocrine hormones guanylin and uroguanylin early in colorectal carcinogenesis. This observation suggests oral replacement with a GUCY2C agonist may be an effective targeted chemoprevention agent. Linaclotide is an FDA-approved oral GUCY2C agonist formulated for gastric release, inducing fluid secretion into the small bowel to treat chronic idiopathic constipation. The ability of oral linaclotide to induce a pharmacodynamic response in epithelial cells of the colorectum in humans remains undefined. Here, we demonstrate that administration of 0.87 mg of oral linaclotide daily for 7 days to healthy volunteers, after oral colon preparation with polyethylene glycol solution (MoviPrep), activates GUCY2C, resulting in accumulation of its product cyclic (c)GMP in epithelial cells of the cecum, transverse colon, and distal rectum. GUCY2C activation by oral linaclotide was associated with homeostatic signaling, including phosphorylation of vasodilator-stimulated phosphoprotein and inhibition of proliferation quantified by reduced Ki67-positive epithelial cells. In the absence of the complete oral colonoscopy preparation, linaclotide did not alter cGMP production in epithelial cells of the colorectum, demonstrating that there was an effect related to the laxative preparation. These data show that the current FDA-approved formulation of oral linaclotide developed for small-bowel delivery to treat chronic idiopathic constipation is inadequate for reliably regulating GUCY2C in the colorectum to prevent tumorigenesis. The study results highlight the importance of developing a novel GUCY2C agonist formulated for release and activity targeted to the large intestine for colorectal cancer prevention. Cancer Prev Res; 10(6); 345-54. ©2017 AACR.

Adenoma detection in excellent versus good bowel preparation for colonoscopy.

GOAL: To determine whether Excellent bowel cleansing is superior to Good for the detection of adenomas. BACKGROUND: High quality colonoscopy requires Adequate bowel preparation. However, it is unknown whether adenoma detection differs between subcategories of Adequate cleansing. STUDY: We utilized a retrospective, cross-sectional study design to obtain data about patients undergoing colonoscopy at a single university center between August 31, 2011 and September 1, 2012. Primary outcome was adenoma detection rate (ADR), the percentage of patients with ≥1 adenoma. Secondary outcomes included adenomas per colonoscopy, adenoma distribution (proximal vs. distal), and detection of advanced adenomas, sessile serrated polyps (SSP), and cancer. RESULTS: The electronic medical record of 5113 consecutive colonoscopies with Good or Excellent preparation was queried for preparation quality, colonoscopy indication, demographics, medical history, and history of adenoma and colon cancer. Exclusion criteria were age below 18 years, inflammatory bowel disease, or familial polyposis. Adenoma detection was not superior with Excellent cleansing as compared with Good for ADR [respectively, 26% vs. 29%, odds ratio 0.97 (0.85, 1.11), P=0.618] or adenomas per colonoscopy [respectively, 0.437 vs. 0.499, incidence rate ratio (IRR) 0.98 (0.90, 1.07), P=0.705]. Excellent cleansing demonstrated superior detection of SSPs [IRR 1.66 (1.14, 2.40), P=0.008] and advanced adenomas [IRR 1.37 (1.09, 1.72), P=0.007] but not colon cancer [odds ratio 0.286 (0.083, 0.985), P=0.0474]. CONCLUSIONS: ADR is not significantly different between the Adequate subcategories of Excellent and Good. However, Excellent cleansing is associated with superior detection of advanced adenomas and SSPs. If confirmed, achieving an Excellent preparation may improve colonoscopy performance in the proximal colon where SSPs primarily occur.

Is single-cell apoptosis sufficient for the diagnosis of graft-versus-host disease in the colon?

Low-grade lesions of graft-versus-host disease (GVHD) in the colon are not uncommon. To determine if minimal diagnostic criteria can be established in such biopsies, we correlated histologic findings with clinical history and investigated the role of endoscopy and electron microscopy in establishing GVHD. About 85 colonic biopsies that were histologically consistent with GVHD from 47 bone-marrow transplant recipients were reviewed retrospectively. Of nine cases showing only a single apoptotic cell in the intestinal epithelium, only four lacked any confounding factors of GVHD. These cases, while too few to assess the utility of finding one apoptotic cell with statistical significance, appear to support the idea that in the appropriate clinical setting, a single apoptotic cell could be reported as possibly representing early GVHD. Endoscopic findings did not reliably correlate with histology. Although electron microscopy can be a useful adjunct, it does not contribute to the diagnosis of GVHD.

Safety of sodium phosphate tablets in patients receiving propofol-based sedation for colonoscopy.

GOALS: To compare the incidence of peri-procedure adverse events in patients undergoing colon cleansing with sodium phosphate tablets or polyethylene glycol solution prior to colonoscopy with propofol-based sedation. BACKGROUND: Propofol is a rapidly acting hypnotic sedative general anesthetic agent increasingly being used for colonoscopy. Although traditionally patients fast overnight prior to a general anesthetic, a new Food and Drug Administration-approved sodium phosphate tablet purgative requires ingestion of 20 tablets with 56 ounces of clear liquid 3 to 5 hours prior to colonoscopy. STUDY: We retrospectively reviewed 97 outpatients who received propofol-based sedation for colonoscopy. This was a subset of a randomized, investigator-blinded, multicenter trial comparing sodium phosphate tablets with polyethylene glycol. Study data and anesthesia records were reviewed for peri-procedure hemodynamic, cardiac, and pulmonary adverse events as well as the need for hospital admission. RESULTS: There were no statistically significant differences between the 2 groups when analyzed for the development of tachycardia, decrease in mean arterial pressure below 50 mmHg, or a reduction in the mean arterial pressure greater than 30% from the pre-procedure value. No patients in either group experienced hypoxia (oxygen saturation < 90%), excessive regurgitation, pneumonia, or hospital admission. CONCLUSIONS: Peri-procedure adverse events occurred rarely and with no increased frequency in patients using the sodium phosphate tablet purgative and receiving propofol-based sedation. The sodium phosphate tablet purgative is safe for patients receiving propofol-based sedation for colonoscopy.