In Search of Nodular Gastric Antral Vascular Ectasia: A Distinct Entity or Simply Hyperplastic Polyps Arising in Gastric Antral Vascular Ectasia?

CONTEXT.­: Nodular gastric antral vascular ectasia (GAVE) is a reported phenotype of GAVE that has histologic features overlapping with gastric hyperplastic polyps (GHPs), with additional features often seen in flat mucosa of GAVE. OBJECTIVE.­: To determine if nodular GAVE and GHPs are distinct lesions by evaluating the prevalence of features reported in nodular GAVE in GHPs with or without associated GAVE. DESIGN.­: A review of all lesions diagnosed as GHPs between 2014 and 2017 was performed. Slides were analyzed for a number of features including established histologic features of GAVE without knowledge of clinical or endoscopic features. RESULTS.­: A total of 90 polyps were analyzed including 18 from patients with GAVE (20%). GAVE polyps were larger than non-GAVE polyps (average size, 1.3 cm versus 0.68 cm; P < .001), with more common extensive ulceration and associated granulation tissue (61.11% [n = 11] versus 4.17% [n = 3]; P = .004), fibrin thrombi (50% [n = 9] versus 15% [n = 11]; P = .003), moderate to marked vascular ectasia (83% [n = 15] versus 35% [n = 11]; P = .001), and fibrohyalinosis (72% [n = 13] versus 28% [n = 20]; P = .001). All polyps showed foveolar hyperplasia and smooth muscle proliferation. There were no features that were exclusively found in GAVE or non-GAVE cases. CONCLUSIONS.­: Nodular GAVE appears to represent GHPs arising in a background of GAVE, with superimposed features found in flat mucosa of GAVE stomachs. The presence of fibrin thrombi, marked vascular ectasia, fibrohyalinosis, and/or ulceration in a GHP is suggestive but not diagnostic of GAVE, and the absence of these features does not rule out GAVE.

Trial marriage model-Female mate choice under male interference.

In sexually reproducing animals, the process of mate choice by females is often mixed with the process of male-male competition. Current models of female male choice focus mainly on how females identify the higher quality of males, but neglect the effect of male-male competition on the mate choice of females. Therefore, it remains controversial what is the relative importance of two processes in forming a social bond. We propose a new 'trial marriage' model for females' mate choice. The model assumes that females unconditionally accept any male they first encounter as their mating partner, and then conditionally switch mates to a new male of higher quality than their current partner when male-male competition occurs. This model was tested in the green weevil Hypomeces squamosus by exploring how females switched mates when males' mating interference was experimentally induced. The likelihood that females switched mates, as well as their conditional acceptance criteria of a new mate, was both raised with the intensity of males' mating interference that was manipulated in an enhanced encounter rate experiment, and in male introduction or stepwise removal experiments. These experimental findings confirm that a 'trial marriage' strategy occurs during females' mate choice. Compared with other strategies, it is more beneficial for females to choose a better mate without paying the costs of identifying males as suggested by the 'trial marriage' strategy. More importantly, using the current partner quality as the conditional acceptance threshold of new mates, females can choose better males in future encounters with potential mates. In the green weevils, males' preference for larger females and the higher possibility of the largest male winning an interference are mixed together when males' mating interference reaches a higher intensity. Therefore, the consequence of a male interference will determine which male could be chosen by a female. Under this condition, conditional acceptance of the winner becomes the most beneficial strategy of females in choosing their mates. We thus suggest that the 'trial marriage' strategy would be more efficient when males' mating interference becomes the determinant factor of females' mate choice.

Dietary Factors in Sulfur Metabolism and Pathogenesis of Ulcerative Colitis.

The biogeography of inflammation in ulcerative colitis (UC) suggests a proximal to distal concentration gradient of a toxin. Hydrogen sulfide (H2S) has long been considered one such toxin candidate, and dietary sulfur along with the abundance of sulfate reducing bacteria (SRB) were considered the primary determinants of H2S production and clinical course of UC. The metabolic milieu in the lumen of the colon, however, is the result of a multitude of factors beyond dietary sulfur intake and SRB abundance. Here we present an updated formulation of the H2S toxin hypothesis for UC pathogenesis, which strives to incorporate the interdependency of diet composition and the metabolic activity of the entire colon microbial community. Specifically, we suggest that the increasing severity of inflammation along the proximal-to-distal axis in UC is due to the dilution of beneficial factors, concentration of toxic factors, and changing detoxification capacity of the host, all of which are intimately linked to the nutrient flow from the diet.

Mailed Outreach Is Superior to Usual Care Alone for Colorectal Cancer Screening in the USA: A Systematic Review and Meta-analysis.

Mailed outreach promoting colorectal cancer (CRC) screening with a stool blood test kit may increase participation, but magnitude and consistency of benefit of this intervention strategy is uncertain. Our aim was to conduct a systematic review and meta-analysis of randomized controlled trials (RCTs) comparing mailed outreach offering stool tests to usual care, clinic-based screening offers on CRC screening uptake in the USA. We performed a systematic literature search of five databases for RCTs of mailed outreach from January 1980 through June 2017. Primary outcome was screening completion, summarized using random-effects meta-analysis as pooled differences in proportion completing the screening and relative risk of achieving screening compared to control. Subgroup analyses by test type offered-fecal immunochemical test (FIT) or guaiac fecal occult blood test (gFOBT), the presence of telephone reminders, and the presence of predominant underserved/minority population within study were performed. Quality of evidence was evaluated using the GRADE framework. Seven RCTs which enrolled 12,501 subjects were included (n = 5703 assigned mailed outreach and n = 6798 usual care). Mailed outreach resulted in a 28% absolute (95% CI 25-30%; I2 = 47%) and a 2.8-fold relative (RR 2.65, 95% CI 2.03-3.45; I2 = 92%) increase in screening completion compared to usual care, with a number needed to invite estimated to be 3.6. Similar outcomes were observed across subgroups. Overall body of evidence was at moderate quality. Mailed outreach offering a gFOBT or FIT is associated with a large and consistent increase in CRC screening completion and should be considered for more widespread implementation for improving screening rates nationwide.

Distribution of Esophageal Motor Disorders in Diabetic Patients With Dysphagia.

BACKGROUND: Diabetes mellitus can cause various gastrointestinal symptoms. Assessment of esophageal dysmotility in diabetic patients has been scarcely studied. The aim of this study was to determine the esophageal motor characteristics of diabetic versus nondiabetic patients who present with dysphagia. METHODS: High-resolution esophageal manometries (HREMs) of 83 diabetic patients and 83 age and gender-matched nondiabetic patients with dysphagia from 2 medical centers were included in this study. Demographic information, medical comorbidities, and medication usage were recorded for each patient in a single registry. HREM of each patient was evaluated and the different functional parameters were recorded. KEY RESULTS: Overall, 46% of diabetic patients were found to have an esophageal motor disorder. Diabetic patients with dysphagia were more likely to have failed swallows on HREM (50.6% vs. 33.7%; P=0.03) as compared with nondiabetic patients. Among diabetic patients, those being treated with insulin were more likely to have failed (69.0% vs. 40.7%; P=0.01) and weak (65.5% vs. 33.3%; P=0.005) swallows as compared with diabetic patients not on insulin. Among diabetic patients, those with abnormal manometry were more likely to demonstrate diabetic retinopathy (27.0% vs. 8.7%; P=0.04). There was a trend toward increased incidence of esophagogastric junction outflow obstruction in diabetic patients (10.8% vs. 2.4%; P=0.057) as compared with nondiabetic patients. CONCLUSIONS: Nearly half of diabetic patients with dysphagia have some type of an esophageal motility disorder. Diabetic retinopathy and the use of insulin are predictive of esophageal motor abnormalities among diabetic patients.

Contained colonic perforation due to cecal retroflexion.

Complications of cecal retroflexion performed during colonoscopy have not previously been reported to occur. We report a case of contained colonic perforation secondary to using cecal retroflexion technique to examine the colon, and review available published reports of complications associated with this technique. We conclude that complications may rarely occur with use of cecal retroflexion, and that the clinical benefit of this technique is uncertain.

Challenges and possible solutions to colorectal cancer screening for the underserved.

Colorectal cancer (CRC) is a leading cause of cancer mortality worldwide. CRC incidence and mortality can be reduced through screening. However, in the United States, screening participation remains suboptimal, particularly among underserved populations such as the uninsured, recent immigrants, and racial/ethnic minority groups. Increasing screening rates among underserved populations will reduce the US burden of CRC. In this commentary focusing on underserved populations, we highlight the public health impact of CRC screening, list key challenges to screening the underserved, and review promising approaches to boost screening rates. We identify four key policy and research priorities to increase screening among underserved populations: 1) actively promote the message, "the best test is the one that gets done"; 2) develop and implement methods to identify unscreened individuals within underserved population groups for screening interventions; 3) develop and implement approaches for organized screening delivery; and 4) fund and enhance programs and policies that provide access to screening, diagnostic follow-up, and CRC treatment for underserved populations. This commentary represents the consensus of a diverse group of experts in cancer control and prevention, epidemiology, gastroenterology, and primary care from across the country who formed the Coalition to Boost Screening among the Underserved in the United States. The group was organized and held its first annual working group meeting in conjunction with the World Endoscopy Organization's annual Colorectal Cancer Screening Committee meeting during Digestive Disease Week 2012 in San Diego, California.

Comparative effectiveness of fecal immunochemical test outreach, colonoscopy outreach, and usual care for boosting colorectal cancer screening among the underserved: a randomized clinical trial.

IMPORTANCE: Colorectal cancer (CRC) screening saves lives, but participation rates are low among underserved populations. Knowledge on effective approaches for screening the underserved, including best test type to offer, is limited. OBJECTIVE: To determine (1) if organized mailed outreach boosts CRC screening compared with usual care and (2) if FIT is superior to colonoscopy outreach for CRC screening participation in an underserved population. DESIGN, SETTING, AND PARTICIPANTS: We identified uninsured patients, not up to date with CRC screening, age 54 to 64 years, served by the John Peter Smith Health Network, Fort Worth and Tarrant County, Texas, a safety net health system. INTERVENTIONS: Patients were assigned randomly to 1 of 3 groups. One group was assigned to fecal immunochemical test (FIT) outreach, consisting of mailed invitation to use and return an enclosed no-cost FIT (n = 1593). A second was assigned to colonoscopy outreach, consisting of mailed invitation to schedule a no-cost colonoscopy (n = 479). The third group was assigned to usual care, consisting of opportunistic primary care visit­based screening (n = 3898). In addition, FIT and colonoscopy outreach groups received telephone follow-up to promote test completion. MAIN OUTCOME MEASURES: Screening participation in any CRC test within 1 year after randomization. RESULTS: Mean patient age was 59 years; 64% of patients were women. The sample was 41% white, 24% black, 29% Hispanic, and 7% other race/ethnicity. Screening participation was significantly higher for both FIT (40.7%) and colonoscopy outreach (24.6%) than for usual care (12.1%) (P < .001 for both comparisons with usual care). Screening was significantly higher for FIT than for colonoscopy outreach (P < .001). In stratified analyses, screening was higher for FIT and colonoscopy outreach than for usual care, and higher for FIT than for colonoscopy outreach among whites, blacks, and Hispanics (P < .005 for all comparisons). Rates of CRC identification and advanced adenoma detection were 0.4% and 0.8% for FIT outreach, 0.4% and 1.3% for colonoscopy outreach, and 0.2% and 0.4% for usual care, respectively (P < .05 for colonoscopy vs usual care advanced adenoma comparison; P > .05 for all other comparisons). Eleven of 60 patients with abnormal FIT results did not complete colonoscopy. CONCLUSIONS AND REVELANCE: Among underserved patients whose CRC screening was not up to date, mailed outreach invitations resulted in markedly higher CRC screening compared with usual care. Outreach was more effective with FIT than with colonoscopy invitation. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01191411.

Implementation of routine screening for Lynch syndrome in university and safety-net health system settings: successes and challenges.

PURPOSE: Routine screening for evidence of DNA mismatch repair abnormalities can identify colorectal cancer patients with Lynch syndrome, but impact in usual care settings requires study. After implementing routine screening at our university and safety-net health systems as usual practice, our aims were to determine outcomes, including screening process quality. METHODS: We conducted a retrospective cohort study from 1 May 2010 to 1 May 2011. Screening included reflexive immunohistochemistry to evaluate DNA mismatch repair protein expression for patients with colorectal cancer aged ≤70 years, with a cancer genetics team following up results. Screening outcomes, as well as challenges to a high-quality screening process were evaluated. RESULTS: We included 129 patients (mean age 56 years, 36% female); 100 had immunohistochemistry screening completed. Twelve patients had abnormal immunohistochemistry: four with definite Lynch syndrome, four with probable Lynch syndrome, and three without Lynch syndrome; one patient had an incomplete work-up. Lynch syndrome was confirmed for 6/13 asymptomatic relatives tested. Screening process quality was optimal for 77.5% of patients. Barriers to optimal quality screening included ensuring reflexive immunohistochemistry completion, complete follow-up of abnormal immunohistochemistry, and timely incorporation of results into clinical decision making. CONCLUSION: Usual care implementation of routine screening for Lynch syndrome can result in significant rates of detection, even in a largely safety-net setting. To optimize implementation, challenges to high-quality Lynch syndrome screening, such as ensuring reflexive screening completion and clinically indicated genetic testing and follow-up for abnormal screens, must be identified and addressed.

Principal component analysis of cerebellar shape on MRI separates SCA types 2 and 6 into two archetypal modes of degeneration.

Although "cerebellar ataxia" is often used in reference to a disease process, presumably there are different underlying pathogenetic mechanisms for different subtypes. Indeed, spinocerebellar ataxia (SCA) types 2 and 6 demonstrate complementary phenotypes, thus predicting a different anatomic pattern of degeneration. Here, we show that an unsupervised classification method, based on principal component analysis (PCA) of cerebellar shape characteristics, can be used to separate SCA2 and SCA6 into two classes, which may represent disease-specific archetypes. Patients with SCA2 (n=11) and SCA6 (n=7) were compared against controls (n=15) using PCA to classify cerebellar anatomic shape characteristics. Within the first three principal components, SCA2 and SCA6 differed from controls and from each other. In a secondary analysis, we studied five additional subjects and found that these patients were consistent with the previously defined archetypal clusters of clinical and anatomical characteristics. Secondary analysis of five subjects with related diagnoses showed that disease groups that were clinically and pathophysiologically similar also shared similar anatomic characteristics. Specifically, Archetype #1 consisted of SCA3 (n=1) and SCA2, suggesting that cerebellar syndromes accompanied by atrophy of the pons may be associated with a characteristic pattern of cerebellar neurodegeneration. In comparison, Archetype #2 was comprised of disease groups with pure cerebellar atrophy (episodic ataxia type 2 (n=1), idiopathic late-onset cerebellar ataxias (n=3), and SCA6). This suggests that cerebellar shape analysis could aid in discriminating between different pathologies. Our findings further suggest that magnetic resonance imaging is a promising imaging biomarker that could aid in the diagnosis and therapeutic management in patients with cerebellar syndromes.