RE.GA.IN.: the Real-world Gastritis Initiative-updating the updates.

At the end of the last century, a far-sighted 'working party' held in Sydney, Australia addressed the clinicopathological issues related to gastric inflammatory diseases. A few years later, an international conference held in Houston, Texas, USA critically updated the seminal Sydney classification. In line with these initiatives, Kyoto Global Consensus Report, flanked by the Maastricht-Florence conferences, added new clinical evidence to the gastritis clinicopathological puzzle.The most relevant topics related to the gastric inflammatory diseases have been addressed by the Real-world Gastritis Initiative (RE.GA.IN.), from disease definitions to the clinical diagnosis and prognosis. This paper reports the conclusions of the RE.GA.IN. consensus process, which culminated in Venice in November 2022 after more than 8 months of intense global scientific deliberations. A forum of gastritis scholars from five continents participated in the multidisciplinary RE.GA.IN. consensus. After lively debates on the most controversial aspects of the gastritis spectrum, the RE.GA.IN. Faculty amalgamated complementary knowledge to distil patient-centred, evidence-based statements to assist health professionals in their real-world clinical practice. The sections of this report focus on: the epidemiology of gastritis; Helicobacter pylori as dominant aetiology of environmental gastritis and as the most important determinant of the gastric oncogenetic field; the evolving knowledge on gastric autoimmunity; the clinicopathological relevance of gastric microbiota; the new diagnostic horizons of endoscopy; and the clinical priority of histologically reporting gastritis in terms of staging. The ultimate goal of RE.GA.IN. was and remains the promotion of further improvement in the clinical management of patients with gastritis.

The use of non-invasive stool tests for verification of Helicobacter pylori eradication and clarithromycin resistance.

BACKGROUND: Clarithromycin resistance of Helicobacter pylori (H. pylori) represents a major challenge in eradication therapy. In this study, we assessed if non-invasive stool tests can be used to verify successful H. pylori eradication and determine clarithromycin resistance. MATERIALS AND METHODS: In this prospective study, patients undergoing urea breath testing (UBT) for confirmation of H. pylori eradication were asked to collect the stool as both a dry fecal sample and fecal immunochemical test (FIT). Stool H. pylori antigen testing (SAT) was performed on these samples and assessed for its accuracy in eradication verification. Type and duration of antibiotic treatment were retrospectively collected from patient records and compared with clarithromycin resistance determined by PCR of stool samples. RESULTS: H. pylori eradication information was available for a total of 145 patients (42.7% male, median age: 51.2). Successful eradication was achieved in 68.1% of patients. SAT on FIT samples had similar accuracy for eradication assessment compared to dry fecal samples, 72.1% [95% CI 61.4-81.2] versus 72.2% [95% CI 60.9-81.7]. Clarithromycin resistance rate was 13.4%. CONCLUSION: H. pylori antigen testing on FIT stool samples to verify H. pylori eradication is feasible and has similar accuracy as H. pylori antigen testing on dry stool samples. Dry stool, but not FIT, was suitable for non-invasive identification of H. pylori clarithromycin resistance by rt-PCR personalizing antibiotic treatment strategies without the need for invasive diagnostics is desirable, as the cure rate of first-line empirical H. pylori treatment remains low.

Gastric Intestinal Metaplasia: Real Culprit or Innocent Bystander as a Precancerous Condition for Gastric Cancer?

Gastric intestinal metaplasia (GIM), which denotes conversion of gastric mucosa into an intestinal phenotype, can occur in all regions of the stomach, including cardiac, fundic, and pyloric mucosa. Since the earliest description of GIM, its association with gastric cancer of the differentiated (intestinal) type has been a well-recognized concern. Many epidemiologic studies have confirmed GIM to be significantly associated with subsequent gastric cancer development. Helicobacter pylori, the principal etiologic factor for gastric cancer, plays the most important role in predisposing to GIM. Although the role of GIM in the stepwise progression model of gastric carcinogenesis (the so-called "Correa cascade") has come into question recently, we review the scientific evidence that strongly supports this long-standing model and propose a new progression model that builds on the Correa cascade. Eradication of H pylori is the most important method for preventing gastric cancer globally, but the effect of eradication on established GIM, is limited, if any. Endoscopic surveillance for GIM may, therefore, be necessary, especially when there is extensive corpus GIM. Recent advances in image-enhanced endoscopy with integrated artificial intelligence have facilitated the identification of GIM and neoplastic lesions, which will impact preventive strategies in the near future.

Young-onset colorectal cancer.

In the past decades the incidence of colorectal cancer (CRC) in people under the age of 50 years has increased, which is referred to as early-onset CRC or young-onset CRC (YO-CRC). YO-CRC is expected to account for 11% of colon cancers and 23% of rectal cancers by 2030. This trend is observed in different parts of the world and in both men and women. In 20% of patients with YO-CRC, a hereditary cancer syndrome is found as the underlying cause; however, in the majority of patients no genetic predisposition is present. Beginning in the 1950s, major changes in lifestyle such as antibiotic use, low physical activity and obesity have affected the gut microbiome and may be an important factor in YO-CRC development. Owing to a lack of screening, patients with YO-CRC are often diagnosed with advanced-stage disease. Long-term treatment-related complications should be taken into account in these younger patients, making the more traditional sequential approaches of drug therapy not always the most appropriate option. To better understand the underlying mechanism and define relationships between environmental factors and YO-CRC development, long-term prospective studies are needed with lifestyle data collected from childhood.

Faecal occult blood loss accurately predicts future detection of colorectal cancer. A prognostic model.

OBJECTIVES: To examine the prognostic potential of repeated faecal haemoglobin (F-Hb) concentration measurements in faecal immunochemical test (FIT)-based screening for colorectal cancer (CRC). DESIGN: Prognostic model. SETTING: Dutch biennial FIT-based screening programme during 2014-2018. PARTICIPANTS: 265 881 participants completing three rounds of FIT, with negative test results (F-Hb <47 µg Hb/g faeces) in rounds 1 and 2. INTERVENTIONS: Colonoscopy follow-up in participants with a positive FIT (F-Hb ≥47 µg Hb/g faeces). MAIN OUTCOMES: We evaluated prognostic models for detecting advanced neoplasia (AN) and CRC in round 3, with as predictors, participant age, sex, F-Hb in rounds 1 and 2, and categories/combinations/non-linear transformations of F-Hb. Primary evaluation criteria included: risk prediction accuracy (calibration), discrimination of participants with versus without AN or CRC (optimism-adjusted C-statistics, range 0.5-1.0), the degree of risk stratification and C-statistics in external validation. RESULTS: Among study participants, 8806 (3.3%) had a positive FIT result, 3254 (1.2%) had AN detected and 557 (0.2%) had cancer. F-Hb concentrations in rounds 1 and 2 were the strongest outcome predictors, with adjusted ORs of up to 9.4 (95% CI 7.5 to 11.7) for the highest F-Hb category. Risk predictions matched the observed risk for most participants (calibration intercept -0.008 to -0.099; slope 0.982-0.998), and discriminated participants with versus without AN or CRC with C-statistics of 0.78 (95% CI 0.77 to 0.79) and 0.73 (95% CI 0.71 to 0.75), respectively. The predicted risk ranged from 0.4% to 36.7% for AN and from 0.0% to 5.5% for CRC across participants. In external validation, the model retained similar discrimination accuracy for AN (C-statistic 0.77, 95% CI 0.66 to 0.87) and CRC (C-statistic 0.78, 95% CI 0.66 to 0.91). CONCLUSION: Participants at lower versus higher risk of future AN or CRC can be accurately identified based on their age, sex and particularly, prior F-Hb concentrations. Risk stratification should be considered based on this information.

Effect of Colonoscopy Screening on Risks of Colorectal Cancer and Related Death.

BACKGROUND: Although colonoscopy is widely used as a screening test to detect colorectal cancer, its effect on the risks of colorectal cancer and related death is unclear. METHODS: We performed a pragmatic, randomized trial involving presumptively healthy men and women 55 to 64 years of age drawn from population registries in Poland, Norway, Sweden, and the Netherlands between 2009 and 2014. The participants were randomly assigned in a 1:2 ratio either to receive an invitation to undergo a single screening colonoscopy (the invited group) or to receive no invitation or screening (the usual-care group). The primary end points were the risks of colorectal cancer and related death, and the secondary end point was death from any cause. RESULTS: Follow-up data were available for 84,585 participants in Poland, Norway, and Sweden - 28,220 in the invited group, 11,843 of whom (42.0%) underwent screening, and 56,365 in the usual-care group. A total of 15 participants had major bleeding after polyp removal. No perforations or screening-related deaths occurred within 30 days after colonoscopy. During a median follow-up of 10 years, 259 cases of colorectal cancer were diagnosed in the invited group as compared with 622 cases in the usual-care group. In intention-to-screen analyses, the risk of colorectal cancer at 10 years was 0.98% in the invited group and 1.20% in the usual-care group, a risk reduction of 18% (risk ratio, 0.82; 95% confidence interval [CI], 0.70 to 0.93). The risk of death from colorectal cancer was 0.28% in the invited group and 0.31% in the usual-care group (risk ratio, 0.90; 95% CI, 0.64 to 1.16). The number needed to invite to undergo screening to prevent one case of colorectal cancer was 455 (95% CI, 270 to 1429). The risk of death from any cause was 11.03% in the invited group and 11.04% in the usual-care group (risk ratio, 0.99; 95% CI, 0.96 to 1.04). CONCLUSIONS: In this randomized trial, the risk of colorectal cancer at 10 years was lower among participants who were invited to undergo screening colonoscopy than among those who were assigned to no screening. (Funded by the Research Council of Norway and others; NordICC ClinicalTrials.gov number, NCT00883792.).

Adenoma Detection Rate and Risk for Interval Postcolonoscopy Colorectal Cancer in Fecal Immunochemical Test-Based Screening : A Population-Based Cohort Study.

BACKGROUND: The adenoma detection rate (ADR) is an essential quality indicator for endoscopists performing colonoscopies for colorectal cancer (CRC) screening as it is associated with postcolonoscopy CRCs (PCCRCs). Currently, data on ADRs of endoscopists performing colonoscopies in fecal immunochemical testing (FIT)-based screening, the most common screening method, are scarce. Also, the association between the ADR and PCCRC has not been demonstrated in this setting. OBJECTIVE: To evaluate the association between the ADR and PCCRC risk in colonoscopies done after a positive FIT result. DESIGN: Population-based cohort. SETTING: Dutch, FIT-based, CRC screening program. PARTICIPANTS: Patients undergoing colonoscopy, done by accredited endoscopists, after a positive FIT result. MEASUREMENTS: Quality indicator performance and PCCRC incidence for colonoscopies in FIT-positive screenees were assessed. The PCCRCs were classified as interval, a cancer detected before recommended surveillance, or noninterval. The association between ADR and interval PCCRC was evaluated with a multivariable Cox regression model and PCCRC incidence was determined for different ADRs. RESULTS: 362 endoscopists performed 116 360 colonoscopies with a median ADR of 67%. In total, 209 interval PCCRCs were identified. The ADR was associated with interval PCCRC, with an adjusted hazard ratio of 0.95 (95% CI, 0.92 to 0.97) per 1% increase in ADR. For every 1000 patients undergoing colonoscopy, the expected number of interval PCCRC diagnoses after 5 years was approximately 2 for endoscopists with ADRs of 70%, compared with more than 2.5, almost 3.5, and more than 4.5 for endoscopists with ADRs of 65%, 60%, and 55%, respectively. LIMITATION: The relative short duration of follow-up (median, 52 months) could be considered a limitation. CONCLUSION: The ADR of endoscopists is inversely associated with the risk for interval PCCRC in FIT-positive colonoscopies. Endoscopists performing colonoscopy in FIT-based screening should aim for markedly higher ADRs compared with primary colonoscopy. PRIMARY FUNDING SOURCE: None.

Artificial Intelligence in Colon Capsule Endoscopy-A Systematic Review.

Background and aims: The applicability of colon capsule endoscopy in daily practice is limited by the accompanying labor-intensive reviewing time and the risk of inter-observer variability. Automated reviewing of colon capsule endoscopy images using artificial intelligence could be timesaving while providing an objective and reproducible outcome. This systematic review aims to provide an overview of the available literature on artificial intelligence for reviewing colonic mucosa by colon capsule endoscopy and to assess the necessary action points for its use in clinical practice. Methods: A systematic literature search of literature published up to January 2022 was conducted using Embase, Web of Science, OVID MEDLINE and Cochrane CENTRAL. Studies reporting on the use of artificial intelligence to review second-generation colon capsule endoscopy colonic images were included. Results: 1017 studies were evaluated for eligibility, of which nine were included. Two studies reported on computed bowel cleansing assessment, five studies reported on computed polyp or colorectal neoplasia detection and two studies reported on other implications. Overall, the sensitivity of the proposed artificial intelligence models were 86.5-95.5% for bowel cleansing and 47.4-98.1% for the detection of polyps and colorectal neoplasia. Two studies performed per-lesion analysis, in addition to per-frame analysis, which improved the sensitivity of polyp or colorectal neoplasia detection to 81.3-98.1%. By applying a convolutional neural network, the highest sensitivity of 98.1% for polyp detection was found. Conclusion: The use of artificial intelligence for reviewing second-generation colon capsule endoscopy images is promising. The highest sensitivity of 98.1% for polyp detection was achieved by deep learning with a convolutional neural network. Convolutional neural network algorithms should be optimized and tested with more data, possibly requiring the set-up of a large international colon capsule endoscopy database. Finally, the accuracy of the optimized convolutional neural network models need to be confirmed in a prospective setting.

Third Asia-Pacific consensus recommendations on colorectal cancer screening and postpolypectomy surveillance.

The Asia-Pacific region has the largest number of cases of colorectal cancer (CRC) and one of the highest levels of mortality due to this condition in the world. Since the publishing of two consensus recommendations in 2008 and 2015, significant advancements have been made in our knowledge of epidemiology, pathology and the natural history of the adenoma-carcinoma progression. Based on the most updated epidemiological and clinical studies in this region, considering literature from international studies, and adopting the modified Delphi process, the Asia-Pacific Working Group on Colorectal Cancer Screening has updated and revised their recommendations on (1) screening methods and preferred strategies; (2) age for starting and terminating screening for CRC; (3) screening for individuals with a family history of CRC or advanced adenoma; (4) surveillance for those with adenomas; (5) screening and surveillance for sessile serrated lesions and (6) quality assurance of screening programmes. Thirteen countries/regions in the Asia-Pacific region were represented in this exercise. International advisors from North America and Europe were invited to participate.

Constitutive programmed death ligand 1 expression protects gastric G-cells from Helicobacter pylori-induced inflammation.

INTRODUCTION: Gastric intestinal metaplasia (GIM) is a premalignant lesion, highly associated with Helicobacter pylori infection. Previous studies have shown that H. pylori is able to induce the expression of programmed death ligand 1 (PD-L1), an inhibitory immune modulator, in gastric cells. Our aim was to investigate whether tissues from GIM patients may exploit PD-L1 expression upon H. pylori infection to evade immunosurveillance. METHODS: Immunohistochemistry was performed for PD-L1 and enteroendocrine markers somatostatin and gastrin on samples derived from a cohort of patients with known GIM, both before and after H. pylori eradication. To determine the identity of any observed PD-L1-positive cells, we performed multiplex immunofluorescent staining and analysis of single-cell sequencing data. RESULTS: GIM tissue was rarely positive for PD-L1. In normal glands from GIM patients, PD-L1 was mainly expressed by gastrin-positive G-cells. While the D-cell and G-cell compartments were both diminished 2-fold (p = .015 and p = .01, respectively) during H. pylori infection in the normal antral tissue of GIM patients, they were restored 1 year after eradication. The total number of PD-L1-positive cells was not affected by H. pylori, but the percentage of PD-L1-positive G-cells was 30% higher in infected subjects (p = .011), suggesting that these cells are preferentially rescued from destruction. CONCLUSIONS: Antral G-cells frequently express PD-L1 during homeostasis. G-cells seem to be protected from H. pylori-induced immune destruction by PD-L1 expression. GIM itself does not express PD-L1 and is unlikely to escape immunosurveillance via expression of PD-L1.

Guaiac-based faecal occult blood tests versus faecal immunochemical tests for colorectal cancer screening in average-risk individuals.

BACKGROUND: Worldwide, many countries have adopted colorectal cancer (CRC) screening programmes, often based on faecal occult blood tests (FOBTs). CRC screening aims to detect advanced neoplasia (AN), which is defined as CRC or advanced adenomas. FOBTs fall into two categories based on detection technique and the detected blood component: qualitative guaiac-based FOBTs (gFOBTs) and faecal immunochemical tests (FITs), which can be qualitative and quantitative. Screening with gFOBTs reduces CRC-related mortality. OBJECTIVES: To compare the diagnostic test accuracy of gFOBT and FIT screening for detecting advanced colorectal neoplasia in average-risk individuals. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, BIOSIS Citation Index, Science Citation Index Expanded, and Google Scholar. We searched the reference lists and PubMed-related articles of included studies to identify additional studies. SELECTION CRITERIA: We included prospective and retrospective studies that provided the number of true positives, false positives, false negatives, and true negatives for gFOBTs, FITs, or both, with colonoscopy as reference standard. We excluded case-control studies. We included studies in which all participants underwent both index test and reference standard ("reference standard: all"), and studies in which only participants with a positive index test underwent the reference standard while participants with a negative test were followed for at least one year for development of interval carcinomas ("reference standard: positive"). The target population consisted of asymptomatic, average-risk individuals undergoing CRC screening. The target conditions were CRC and advanced neoplasia (advanced adenomas and CRC combined). DATA COLLECTION AND ANALYSIS: Two review authors independently screened and selected studies for inclusion. In case of disagreement, a third review author made the final decision. We used the Rutter and Gatsonis hierarchical summary receiver operating characteristic model to explore differences between tests and identify potential sources of heterogeneity, and the bivariate hierarchical model to estimate sensitivity and specificity at common thresholds: 10 µg haemoglobin (Hb)/g faeces and 20 µg Hb/g faeces. We performed indirect comparisons of the accuracy of the two tests and direct comparisons when both index tests were evaluated in the same population. MAIN RESULTS: We ran the initial search on 25 June 2019, which yielded 63 studies for inclusion. We ran a top-up search on 14 September 2021, which yielded one potentially eligible study, currently awaiting classification. We included a total of 33 "reference standard: all" published articles involving 104,640 participants. Six studies evaluated only gFOBTs, 23 studies evaluated only FITs, and four studies included both gFOBTs and FITs. The cut-off for positivity of FITs varied between 2.4 µg and 50 µg Hb/g faeces. For each Quality Assessment of Diagnostic Accuracy Studies (QUADAS)-2 domain, we assessed risk of bias as high in less than 20% of studies. The summary curve showed that FITs had a higher discriminative ability than gFOBTs for AN (P < 0.001) and CRC (P = 0.004). For the detection of AN, the summary sensitivity of gFOBTs was 15% (95% confidence interval (CI) 12% to 20%), which was significantly lower than FITs at both 10 µg and 20 µg Hb/g cut-offs with summary sensitivities of 33% (95% CI 27% to 40%; P < 0.001) and 26% (95% CI 21% to 31%, P = 0.002), respectively. Results were simulated in a hypothetical cohort of 10,000 screening participants with 1% CRC prevalence and 10% AN prevalence. Out of 1000 participants with AN, gFOBTs missed 850, while FITs missed 670 (10 µg Hb/g cut-off) and 740 (20 µg Hb/g cut-off). No significant differences in summary specificity for AN detection were found between gFOBTs (94%; 95% CI 92% to 96%), and FITs at 10 µg Hb/g cut-off (93%; 95% CI 90% to 95%) and at 20 µg Hb/g cut-off (97%; 95% CI 95% to 98%). So, among 9000 participants without AN, 540 were offered (unnecessary) colonoscopy with gFOBTs compared to 630 (10 µg Hb/g) and 270 (20 µg Hb/g) with FITs. Similarly, for the detection of CRC, the summary sensitivity of gFOBTs, 39% (95% CI 25% to 55%), was significantly lower than FITs at 10 µg and 20 µg Hb/g cut-offs: 76% (95% CI 57% to 88%: P = 0.001) and 65% (95% CI 46% to 80%; P = 0.035), respectively. So, out of 100 participants with CRC, gFOBTs missed 61, and FITs missed 24 (10 µg Hb/g) and 35 (20 µg Hb/g). No significant differences in summary specificity for CRC were found between gFOBTs (94%; 95% CI 91% to 96%), and FITs at the 10 µg Hb/g cut-off (94%; 95% CI 87% to 97%) and 20 µg Hb/g cut-off (96%; 95% CI 91% to 98%). So, out of 9900 participants without CRC, 594 were offered (unnecessary) colonoscopy with gFOBTs versus 594 (10 µg Hb/g) and 396 (20 µg Hb/g) with FITs. In five studies that compared FITs and gFOBTs in the same population, FITs showed a higher discriminative ability for AN than gFOBTs (P = 0.003). We included a total of 30 "reference standard: positive" studies involving 3,664,934 participants. Of these, eight were gFOBT-only studies, 18 were FIT-only studies, and four studies combined both gFOBTs and FITs. The cut-off for positivity of FITs varied between 5 µg to 250 µg Hb/g faeces. For each QUADAS-2 domain, we assessed risk of bias as high in less than 20% of studies. The summary curve showed that FITs had a higher discriminative ability for detecting CRC than gFOBTs (P < 0.001). The summary sensitivity for CRC of gFOBTs, 59% (95% CI 55% to 64%), was significantly lower than FITs at the 10 µg Hb/g cut-off, 89% (95% CI 80% to 95%; P < 0.001) and the 20 µg Hb/g cut-off, 89% (95% CI 85% to 92%; P < 0.001). So, in the hypothetical cohort with 100 participants with CRC, gFOBTs missed 41, while FITs missed 11 (10 µg Hb/g) and 11 (20 µg Hb/g). The summary specificity of gFOBTs was 98% (95% CI 98% to 99%), which was higher than FITs at both 10 µg and 20 µg Hb/g cut-offs: 94% (95% CI 92% to 95%; P < 0.001) and 95% (95% CI 94% to 96%; P < 0.001), respectively. So, out of 9900 participants without CRC, 198 were offered (unnecessary) colonoscopy with gFOBTs compared to 594 (10 µg Hb/g) and 495 (20 µg Hb/g) with FITs. At a specificity of 90% and 95%, FITs had a higher sensitivity than gFOBTs. AUTHORS' CONCLUSIONS: FITs are superior to gFOBTs in detecting AN and CRC in average-risk individuals. Specificity of both tests was similar in "reference standard: all" studies, whereas specificity was significantly higher for gFOBTs than FITs in "reference standard: positive" studies. However, at pre-specified specificities, the sensitivity of FITs was significantly higher than gFOBTs.

Predictors of Gastrointestinal Transit Times in Colon Capsule Endoscopy.

INTRODUCTION: Optimizing the accuracy of colon capsule endoscopy (CCE) requires high completion rates. To prevent incomplete CCE, we aimed to identify predictors associated with slow CCE transit times. METHODS: In this population-based study, participants received CCE with a split-dose polyethylene glycol bowel preparation and booster regimen (0.5 L oral sulfate solution and 10 mg metoclopramide if capsule remained in stomach for > 1 hour). The following predictors were assessed: age, sex, body mass index (BMI), smoking, coffee and fiber intake, diet quality, physical activity, dyspeptic complaints, stool pattern, history of abdominal surgery, medication use, and CCE findings. Multivariable logistic and linear regressions with backward elimination were performed. RESULTS: We analyzed 451 CCE procedures with a completion rate of 51.9%. The completion rate was higher among older participants (odds ratio [OR] 1.54, 95% confidence interval [CI] 1.04-2.28, P = 0.03) and participants with a changed stool pattern (OR 2.27, 95% CI 1.20-4.30, P = 0.01). Participants with a history of abdominal surgery had a lower completion rate (OR 0.54, 95% CI 0.36-0.80, P = 0.003). Participants with higher BMI had faster stomach, small bowel, and total transit times (ß = -0.10, P = 0.01; ß = -0.14, P = 0.001; ß = -0.12, P = 0.01). A faster small bowel transit was found in participants with a changed stool pattern (ß = -0.08, P = 0.049) and the use of metoclopramide (ß = -0.14, P = 0.001). Participants with high fiber intake had a slower colonic transit (ß = 0.11, P = 0.03). DISCUSSION: Younger age, unchanged stool pattern, history of abdominal surgery, low BMI, and high fiber intake resulted in slower CCE transit times and lower completion rates. In future practice, these factors can be considered to adjust preparation protocols.

Risk of heart failure among colon and rectal cancer survivors: a population-based case-control study.

AIMS: This population-based case-control study aims to investigate the occurrence of heart failure (HF) among colon and rectal cancer survivors compared with a cancer-free control population taking into account pre-existing cardiovascular risk factors and the influence of treatment. METHODS AND RESULTS: Colon and rectal cancer survivors diagnosed between 2007 and 2014 were selected from a linked cohort of cancer and primary care data in the Netherlands and matched based on gender, birth year, general practitioner (GP) practice, and follow-up period to cancer-free controls. The occurrence of HF was identified based on GP recorded diagnoses after index date (diagnosis date for cases). A Cox proportional hazards model was used to estimate hazard ratios (HRs), adjusted for age, sex, hypertension, diabetes, and hypercholesterolaemia. A total of 5333 colon cancer cases and 2468 rectal cancer cases could be matched to a total of 31 204 cancer-free controls. A statistically significant increased risk of HF was seen among all cases compared with cancer-free controls (HR 1.33; 95% confidence interval: 1.12-1.59). This was also seen when analysing colon cancer and rectal cancer separately. Being diagnosed with stage IV cancer, having hypertension, or having hypercholesterolaemia statistically significantly increased the risk of HF among colon cancer. Hypertension was a statistically significant risk factor for developing HF among rectal cancer cases. CONCLUSIONS: Colon and rectal cancer survivors are at increased risk for developing HF. More awareness should be created by treating physicians and GPs for this potential increased risk in order to further improve survival.

Socioeconomic differences in participation and diagnostic yield within the Dutch national colorectal cancer screening programme with faecal immunochemical testing.

BACKGROUND: CRC mortality rates are higher for individuals with a lower socioeconomic status (SES). Screening could influence health inequalities. We therefore aimed to investigate SES differences in participation and diagnostic yield of FIT screening. METHODS: All invitees in 2014 and 2015 in the Dutch national CRC screening programme were included in the analyses. We used area SES as a measure for SES and divided invitees into quintiles, with Quintile 1 being the highest SES. Logistic regression analysis was used to compare the participation rate, positivity rate, colonoscopy uptake, positive predictive value (PPV) and detection rate across the SES groups. RESULTS: Participation to FIT screening was significantly lower for Quintile 5 (67.0%) compared to the other Quintiles (73.0% to 75.1%; adjusted OR quintile 5 versus quintile 1: 0.73, 95%CI: 0.72-0.74), as well as colonoscopy uptake after a positive FIT (adjusted OR 0.73, 95%CI: 0.69-0.77). The detection rate per FIT participant for advanced neoplasia gradually increased from 3.3% in Quintile 1 to 4.0% in Quintile 5 (adjusted OR 1.20%, 95%CI 1.16-1.24). As a result of lower participation, the yield per invitee was similar for Quintile 5 (2.04%) and Quintile 1 (2.00%), both being lower than Quintiles 2 to 4 (2.20%-2.28%). CONCLUSIONS: Screening has the potential to reduce health inequalities in CRC mortality, because of a higher detection in participants with a lower SES. However, in the Dutch screening programme, this is currently offset by the lower participation in this group.

Use of topical mineral powder as monotherapy for treatment of active peptic ulcer bleeding.

BACKGROUND AND AIMS: The aim of this study was to evaluate the safety and effectiveness of Hemospray (Cook Medical, Winston-Salem, NC, USA), a hemostatic powder, as monotherapy for active peptic ulcer bleeding. METHODS: In this prospective, multicenter, single-arm study, patients with Forrest Ia or Ib peptic ulcers underwent endoscopic application of Hemospray as treatment of first intent. Effectiveness endpoints were successful hemostasis at the end of the index endoscopy, recurrent bleeding within 72 hours and from 72 hours to 30 days, adverse events requiring reintervention or resulting in morbidity or mortality, and 30-day mortality. RESULTS: Hemospray was successfully administered in 98.5% of patients (66/67). Hemostasis was achieved at the index endoscopy in 90.9% of patients (60/66) with Hemospray alone and in an additional 4 patients treated with additional modalities, yielding an overall hemostasis rate of 97.0% (64/66). Rebleeding occurred in 13.3% of patients (8/60), 5 within 72 hours and 3 between 72 hours and 30 days. Two cases of perforation and 2 patient deaths occurred during the study, but none of these cases or any other adverse events were attributed to the use of Hemospray. The rate of early rebleeding was significantly higher in patients with Forrest Ia ulcers compared with patients with Forrest Ib ulcers. Higher rates of early bleeding in patients with Forrest Ia ulcers is consistent with results from studies where Hemospray was used as rescue after failure of conventional methods. CONCLUSIONS: Hemospray is an effective initial treatment for patients with active peptic ulcer bleeding, but care should be taken to monitor for recurrent bleeding. (Clinical trial registration number: NCT01306864.).

Toll-Like Receptor 1 Locus Re-examined in a Genome-Wide Association Study Update on Anti-Helicobacter pylori IgG Titers.

BACKGROUND & AIMS: A genome-wide significant association between anti-Helicobacter pylori (H pylori) IgG titers and Toll-like receptor (TLR1/6/10) locus on 4p14 was demonstrated for individuals of European ancestry, but not uniformly replicated. We re-investigated this association in an updated genome-wide association study (GWAS) meta-analysis for populations with low gastric cancer incidence, address potential causes of cohort heterogeneity, and explore functional implications of genetic variation at the TLR1/6/10 locus. METHODS: The dichotomous GWAS (25% individuals exhibiting highest anti-H pylori IgG titers vs remaining 75%) included discovery and replication sampls of, respectively, n = 15,685 and n = 9676, all of European ancestry. Longitudinal analysis of serologic data was performed on H pylori-eradicated subjects (n = 132) and patients under surveillance for premalignant gastric lesions (n = 107). TLR1/6/10 surface expression, TLR1 mRNA, and cytokine levels were measured in leukocyte subsets of healthy subjects (n = 26) genotyped for TLR1/6/10 variants. RESULTS: The association of the TLR1/6/10 locus with anti-H pylori IgG titers (rs12233670; ß = -0.267 ± SE 0.034; P = 4.42 × 10-15) presented with high heterogeneity and failed replication. Anti-H pylori IgG titers declined within 2-4 years after eradication treatment (P = 0.004), and decreased over time in patients with premalignant gastric lesions (P < 0.001). Variation at the TLR1/6/10 locus affected TLR1-mediated cytokine production and TLR1 surface expression on monocytes (P = 0.016) and neutrophils (P = 0.030), but not mRNA levels. CONCLUSIONS: The association between anti-H pylori IgG titers and TLR1/6/10 locus was not replicated across cohorts, possibly owing to dependency of anti-H pylori IgG titers on therapy, clearance, and antibody decay. H pylori-mediated immune cell activation is partly mediated via TLR1 signaling, which in turn is affected by genetic variation.

Population-Based Prevalence of Gastrointestinal Abnormalities at Colon Capsule Endoscopy.

BACKGROUND & AIMS: The population prevalence of gastrointestinal (GI) disease is unclear and difficult to assess in an asymptomatic population. The aim of this study was to determine prevalence of GI lesions in a largely asymptomatic population undergoing colon capsule endoscopy (CCE). METHODS: Participants aged between 50-75 years were retrieved from the Rotterdam Study, a longitudinal epidemiological study, between 2017-2019. Participants received CCE with bowel preparation. Abnormalities defined as clinically relevant were Barrett segment >3cm, severe ulceration, polyp >10 mm or ≥3 polyps in small bowel (SB) or colon, and cancer. RESULTS: Of 2800 invited subjects, 462 (16.5%) participants (mean age 66.8 years, female 53.5%) ingested the colon capsule. A total of 451 videos were analyzed, and in 94.7% the capsule reached the descending colon. At least 1 abnormal finding was seen in 448 (99.3%) participants. The prevalence of abnormalities per GI segment, and the most common type of abnormality, were as follows: Esophageal 14.8% (Barrett's esophagus <3 cm in 8.3%), gastric 27.9% (fundic gland polyps in 18.1%), SB abnormalities 33.9% (erosions in 23.8%), colon 93.3% (diverticula in 81.2%). A total of 54 participants (12%) had clinically relevant abnormalities, 3 (0.7%) in esophagus/stomach (reflux esophagitis grade D, Mallory Weiss lesion and severe gastritis), 5 (1.1%) in SB (polyps > 10 mm; n = 4, severe ulcer n = 1,) and 46 (10.2%) in colon (polyp > 10 mm or ≥3 polyps n = 46, colorectal cancer n = 1). CONCLUSIONS: GI lesions are very common in a mostly asymptomatic Western population, and clinically relevant lesions were found in 12% at CCE. These findings provide a frame of reference for the prevalence rates of GI lesions in the general population.

A population-based linked cohort of cancer and primary care data: A new source to study the management of cancer in primary care.

OBJECTIVE: Insight into the management of cancer in the primary care setting is pivotal to improve early recognition and survival of cancer patients. Therefore, the Netherlands Cancer Registry (NCR) was linked to the General Practitioner (GP) Database of the PHARMO Database Network to make this research possible. METHODS: The NCR collects tumour data on all newly diagnosed cancer patients, whereas the GP Database comprises data from electronic patient records registered by GPs. Databases were linked using a probabilistic record linkage technology. RESULTS: Through record linkage of the NCR and the GP Database, we have established a large population-based cohort (NCR-PHARMO GP cohort) of 135,868 cancer patients. Data are available on demographics, tumour characteristics, primary health care use before and after cancer diagnosis including medication use, medical conditions, laboratory tests, and referrals. Data can be used for a number of different studies, for example, to study the diagnostic pathway in the primary care setting in order to identify possibilities for early recognition. CONCLUSION: The NCR-PHARMO GP cohort provides rich data on the primary care management of cancer facilitating large-scale observational cancer research in the primary care setting. The patient-level linkage allows for long-term follow-up of cancer patients, with ongoing annual updates.