Improving Adherence to Clinical Practice Guidelines for Managing Gastric Intestinal Metaplasia Among Gastroenterologists at a US Academic Institution.

BACKGROUND: Clinical guidelines reserve endoscopic surveillance after a gastric intestinal metaplasia (GIM) diagnosis for high-risk patients. However, it is unclear how closely guidelines are followed in clinical practice. We examined the effectiveness of a standardized protocol for the management of GIM among gastroenterologists at a US hospital. METHODS: This was a preintervention and postintervention study, which included developing a protocol and education of gastroenterologists on GIM management. For the preintervention study, 50 patients with GIM were randomly selected from a histopathology database at the Houston VA Hospital between January 2016 and December 2019. For the postintervention study, we assessed change in GIM management in a cohort of 50 patients with GIM between April 2020 and January 2021 and surveyed 10 gastroenterologists. The durability of the intervention was assessed in a cohort of 50 GIM patients diagnosed between April 2021 and July 2021. RESULTS: In the preintervention cohort, GIM location was specified (antrum and corpus separated) in 11 patients (22%), and Helicobacter pylori testing was recommended in 11 of 26 patients (42%) without previous testing. Gastric mapping biopsies were recommended in 14% and surveillance endoscopy in 2%. In the postintervention cohort, gastric biopsy location was specified in 45 patients (90%, P <0.001) and H. pylori testing was recommended in 26 of 27 patients without prior testing (96%, P <0.001). Because gastric biopsy location was known in 90% of patients ( P <0.001), gastric mapping was not necessary, and surveillance endoscopy was recommended in 42% ( P <0.001). One year after the intervention, all metrics remained elevated compared with the preintervention cohort. CONCLUSIONS: GIM management guidelines are not consistently followed. A protocol for GIM management and education of gastroenterologists increased adherence to H. pylori testing and GIM surveillance recommendations.

Trends in the incidence of early-onset colorectal cancer in all 50 United States from 2001 through 2017.

BACKGROUND: The rate of change in the incidence of colorectal cancer (CRC) among persons younger than 50 years in the United States appears to vary by demographics, tumor location, and geography. This study analyzed data from all 50 states to examine recent changes in the incidence of CRC among persons younger than 50 years and to identify key subgroups with disproportionate risk. METHODS: Annual incidence rates for CRC, colon cancer, and rectal cancer in persons aged 20 to 49 years were extracted from the US Cancer Statistics for the period 2001-2017. Secular trends were examined overall and by age group, sex, race/ethnicity, stage, and state. Joinpoint regression was used to compute annual percent changes and average annual percent changes (AAPCs) as well as corresponding 95% confidence intervals (95% CIs). RESULTS: The incidence of CRC increased by 1.27% (95% CI, 0.95%-1.60%) annually from 2001 to 2012 and by 3.00% (95% CI, 2.06%-3.95%) annually from 2012 to 2017. AAPCs for the period 2001-2017 were higher among persons aged 20 to 24 years (AAPC, 6.62%; 95% CI, 3.86%-9.45%) in comparison with other age groups and higher among non-Hispanic Whites (AAPC, 2.38%; 95% CI, 1.98%-2.79%) in comparison with other racial/ethnic groups. In 2001-2002, only 1 state had an age-standardized incidence rate > 13.0 per 100,000, but this number increased to 32 states by 2016-2017. CONCLUSIONS: CRC rates among US adults aged 20 to 49 years increased from 2001 to 2017, with the fastest increases observed from 2012 to 2017. Increases were observed among the youngest age groups, among non-Hispanic Whites, and in states in the West, Midwest, and Rocky Mountain regions. Increasing rates across all tumor stages suggest a real increase in CRC incidence.

Colorectal cancer screening in African Americans: are we following the guidelines?

PURPOSE: The age at onset, incidence, and mortality rate of colorectal cancer varies among racial groups being highest in African Americans. This increased risk led to the recommendation to begin screening at the age of 45 years. Whether the recommendation for screening of African Americans at an earlier age was implemented is unknown. METHODS: We used data from the Cancer Control Supplement of National Health Interview Survey (NHIS) conducted in the years 2005, 2010, and 2015 to analyze demographic data and use of colorectal screening (colonoscopy, stool heme testing, sigmoidoscopy, computed tomographic colonography) among the US population between the ages of 45-49 years. RESULTS: Data on colorectal screening was available from 6740 individuals; 16.5% were African Americans. Screening test use among African Americans in 2005, 2010, and 2015 was similar to use in Whites (i.e., 15.4% (95% CI 11.4-19.4), 28.4% (95% CI 19.3-30.4) and 20.2% (95% CI 14.8-25.5) vs. 16.9% (95% CI 15.1-18.6), 19.3% (95% CI 16.9-21.7), and 21.4% (95% CI 18.6-24.2) in 2005, 2010 and 2015, respectively. Observed screening test use rates may largely be accounted for by diagnostic exams. CONCLUSION: The recommendation for earlier colorectal screening of African Americans has not yet resulted in increased test utilization. These results emphasize the need for multidisciplinary actions to inform and implement public health policy.

Bowel Preparation for Colonoscopy in 2020: A Look at the Past, Present, and Future.

PURPOSE OF THIS REVIEW: Colorectal cancer is the third most common cancer in the USA. Colonoscopy is considered the gold standard for colorectal cancer screening and can offer both diagnosis and therapy. The bowel preparation remains a significant barrier for patients who need to undergo colonoscopy and is often cited as the most dreaded aspect of the colonoscopy process. Inadequate bowel preparations still occur in 10-25% of colonoscopies, and this in turn can lead to increased procedural times, lower cecal intubation rates, and shorter interval between colonoscopies. From a quality standpoint, it is imperative that we do what we can to decrease the rate of inadequate bowel preparations. This review will focus on recent data regarding bowel preparation and offers a glimpse into what may be coming in the future. RECENT FINDINGS: Recent advances in the field have been made to improve tolerability of bowel preparations and allow for more adequate colonoscopies. Newer, lower volume, flavored preparations, the use of adjuncts, and using split-dose preparations all can help with tolerability, compliance, and, in turn, preparation quality. Edible bowel preparations may become available in the near future. Early data on the use of artificial intelligence for assessment of preparation quality has been promising. Additionally, utilization of smartphone technology for education prior to the bowel preparation has also been shown to improve the adequacy of bowel preparations. CONCLUSIONS: Ongoing efforts to improve the tolerability and palatability of colonoscopy bowel preparations are important from a quality improvement standpoint to ensure the adequacy of colonoscopy. Incorporating patient-specific factors and comorbidities is also an essential aspect of improving the quality of bowel preparation. Leveraging technology to better communicate with and educate patients on the bowel preparation process is likely to play a larger role in the coming years.

Association Between Inflammatory Bowel Disease and Colorectal Cancer Stage of Disease and Survival.

BACKGROUND: Inflammatory bowel disease (IBD) is associated with an increased risk of colorectal cancer (CRC). However, there are few data comparing outcomes between IBD and non-IBD-associated CRC. METHODS: Retrospective cohort study of patients with CRC identified from the Veteran Affairs (VA) Central Cancer Registry from 1998 to 2012 linked to national VA administrative claims to identify patients with IBD using a previously validated algorithm. The association between IBD status and stage of disease and overall risk of death were evaluated using multivariable logistic and Cox regression, respectively. RESULTS: Among 34,570 CRC patients, 217 had IBD. IBD patients were significantly younger for both colon and rectal cancer. IBD patients who developed rectal cancer were significantly more likely to present with locally advanced or metastatic disease (P = 0.007), but there was no difference in stage among patients with colon cancer. This difference persisted after multivariable adjustment (overall-odds ratio [OR] 1.40, 95% confidence interval [1.03-1.90]; colon-OR 1.22 [0.84-1.78]; rectum-OR 2.04 [1.22-3.40]). Total colectomy was more commonly performed among IBD patients. Overall, IBD was associated with a 52% increased risk of death (hazard ratio 1.52 [1.21-1.91]). CONCLUSIONS: Although IBD is associated with more advanced stage at diagnosis for rectal cancer, it is associated with a worse survival primarily in patients with colon cancer. Further work is needed to better understand the reason for these observed differences between IBD and non-IBD patients and to better delineate the impact of endoscopic surveillance on CRC care and outcomes in IBD patients.

Proinflammatory Sulfur-Reducing Bacteria Are More Abundant in Colonic Biopsies of Patients with Microscopic Colitis Compared to Healthy Controls.

BACKGROUND: Microscopic colitis (MC), a subtype of inflammatory bowel disease, is a chronic condition of unknown etiology. Recent evidence has linked MC with intriguing changes in the stool microbiota, which may be linked to disease pathogenesis. The composition of the mucosal microbiome in patients with MC remains unclear. METHODS: We performed a cross-sectional study comparing colonic tissue samples from patients with MC to those of healthy controls at the Michael E. DeBakey VA Medical Center. We included adults older than 18 who underwent a colonoscopy with biopsies to evaluate chronic diarrhea. Cases were defined by histology consistent with MC and controls by the absence of histologic disease. We conducted structured chart review to exclude other gastrointestinal diseases and obtain demographic (age, sex, race) and clinical (duration of symptoms and concurrent medications) information for cases and controls. We extracted bacterial DNA from formalin-fixed paraffin-embedded tissue samples and sequenced the v4 region of the 16S rRNA gene. Operational taxonomic unit (OTU) clustering was performed using UPARSE, and OTUs were assigned using the SILVA database. Statistical analysis was performed in QIIME and LEfSe. Comparisons with FDR-adjusted p values of less than 0.05 were considered statistically significant. RESULTS: We included 20 MC patients and 20 controls with mean ages of 62 and 54, respectively. Most cases were White (95%), 60% had symptoms for greater than 12 months, and 50% were taking PPIs and NSAIDs at the time of their diagnosis. Compared to controls, MC patients had a significant increase in the proinflammatory sulfur-reducing bacterial family Desulfovibrionales. The Coriobacteriaceae family, abundant in the healthy gut, was significantly decreased in MC cases. There was also an increase in the genus Actinomyces in MC patients on PPI and an increase in the class Bacilli among those taking NSAIDs. DISCUSSION: Patients with MC have an increase in the proinflammatory family Desulfovibrionales. Actinomyces and Bacilli were associated with medications (PPI and NSAID) known to increase the risk of MC. Our findings may have important implications for understanding the pathogenesis of MC.

Rare Collision Tumor of the Biliary Tract.

Malignancies of the gallbladder are uncommon in the developed world. Collision tumors are also extremely rare neoplastic phenomena. Given their scarcity, there are no guidelines for treatment, and prognosis is based on the more aggressive tumor type. We present a patient with a collision tumor consisting of signet-ring cholangiocarcinoma and large-cell neuroendocrine gallbladder carcinoma of the biliary tract, and we review the literature pertaining to biliary tract collision tumors and their management.

Long-Acting Beta Agonists Enhance Allergic Airway Disease.

Asthma is one of the most common of medical illnesses and is treated in part by drugs that activate the beta-2-adrenoceptor (ß2-AR) to dilate obstructed airways. Such drugs include long acting beta agonists (LABAs) that are paradoxically linked to excess asthma-related mortality. Here we show that LABAs such as salmeterol and structurally related ß2-AR drugs such as formoterol and carvedilol, but not short-acting agonists (SABAs) such as albuterol, promote exaggerated asthma-like allergic airway disease and enhanced airway constriction in mice. We demonstrate that salmeterol aberrantly promotes activation of the allergic disease-related transcription factor signal transducer and activator of transcription 6 (STAT6) in multiple mouse and human cells. A novel inhibitor of STAT6, PM-242H, inhibited initiation of allergic disease induced by airway fungal challenge, reversed established allergic airway disease in mice, and blocked salmeterol-dependent enhanced allergic airway disease. Thus, structurally related ß2-AR ligands aberrantly activate STAT6 and promote allergic airway disease. This untoward pharmacological property likely explains adverse outcomes observed with LABAs, which may be overcome by agents that antagonize STAT6.

Airway fibrinogenolysis and the initiation of allergic inflammation.

The past 15 years of allergic disease research have produced extraordinary improvements in our understanding of the pathogenesis of airway allergic diseases such as asthma. Whereas it was previously viewed as largely an immunoglobulin E-mediated process, the gradual recognition that T cells, especially Type 2 T helper (Th2) cells and Th17 cells, play a major role in asthma and related afflictions has inspired clinical trials targeting cytokine-based inflammatory pathways that show great promise. What has yet to be clarified about the pathogenesis of allergic inflammatory disorders, however, are the fundamental initiating factors, both exogenous and endogenous, that drive and sustain B- and T-cell responses that underlie the expression of chronic disease. Here we review how proteinases derived from diverse sources drive allergic responses. A central discovery supporting the proteinase hypothesis of allergic disease pathophysiology is the role played by airway fibrinogen, which in part appears to serve as a sensor of unregulated proteinase activity and which, when cleaved, both participates in a novel allergic signaling pathway through Toll-like receptor 4 and forms fibrin clots that contribute to airway obstruction. Unresolved at present is the ultimate source of airway allergenic proteinases. From among many potential candidates, perhaps the most intriguing is the possibility such enzymes derive from airway fungi. Together, these new findings expand both our knowledge of allergic disease pathophysiology and options for therapeutic intervention.

Cleavage of fibrinogen by proteinases elicits allergic responses through Toll-like receptor 4.

Proteinases and the innate immune receptor Toll-like receptor 4 (TLR4) are essential for expression of allergic inflammation and diseases such as asthma. A mechanism that links these inflammatory mediators is essential for explaining the fundamental basis of allergic disease but has been elusive. Here, we demonstrate that TLR4 is activated by airway proteinase activity to initiate both allergic airway disease and antifungal immunity. These outcomes were induced by proteinase cleavage of the clotting protein fibrinogen, yielding fibrinogen cleavage products that acted as TLR4 ligands on airway epithelial cells and macrophages. Thus, allergic airway inflammation represents an antifungal defensive strategy that is driven by fibrinogen cleavage and TLR4 activation. These findings clarify the molecular basis of allergic disease and suggest new therapeutic strategies.