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Gastric cancer (GC) is a leading cause of global mortality but also a cancer whose footprint is highly unequal. This review aims to define global disease epidemiology, critically appraise strategies of prevention and disease attenuation, and assess how these strategies could be applied to improve outcomes from GC in a world of variable risk and disease burden. Strategies of primary prevention focus on improving the detection and eradication of the main environmental risk factor, Helicobacter pylori. In certain countries of high incidence, endoscopic or radiographic screening of the asymptomatic general population has been adopted as a means of secondary prevention. By contrast, identification and targeted surveillance of individuals with precancerous lesions (such as intestinal metaplasia) is being increasingly embraced in nations of low incidence. This review also highlights existing knowledge gaps in GC prevention as well as the role of emerging technologies for early detection and risk stratification. [ABSTRACT FROM AUTHOR]

The prevalence of precursor lesions for gastric cancer (GC) and the differential burden between countries of varying GC risk is not well-understood. We conducted a systematic review and meta-analysis to estimate the global prevalence of precursor lesions. We estimated the prevalence of atrophic gastritis (AG), gastric intestinal metaplasia (IM), and dysplasia in regions with low, medium, and high GC incidence. Because IM is an advanced manifestation of AG, we assessed the prevalence of less advanced precursors, regardless of the presence of more advanced lesions. Prevalence was sub-stratified by Helicobacter pylori infection, symptomatology, and period (<2000, 2000–2010, and >2010). Among the 582 articles that underwent full-text review, 166 studies met inclusion criteria. The global prevalence estimates of AG, IM, and dysplasia were 25.4%, 16.2%, and 2.0%, respectively, on the basis of 126 studies that reported the prevalence of less advanced precursors, regardless of the presence of more advanced lesions. The prevalence of all precursor lesions was higher in high and medium compared with low GC incidence countries (P <.01). Prevalence of AG and IM was significantly higher among H pylori –infected individuals (P <.01) but not statistically different between symptomatic and asymptomatic individuals (P >.17). All precursors demonstrated a secular decrease in prevalence over time. Gastric precursor lesions have differences in prevalence in regions with differential GC incidence and are associated with H pylori infection. Because of the substantial prevalence of precursor lesions in both symptomatic and asymptomatic individuals, symptomatic evaluation may not be sufficient to identify individuals at risk. These estimates provide important insights for tailoring GC prevention strategies. [Display omitted] [ABSTRACT FROM AUTHOR]

Prior investigations of the impact of case delays on adenoma detection rates have not found a significant association, though these studies included modest delays, with few cases delayed by more than one hour. The aim of this study was to measure the impact of prolonged case delays on the colonoscopy outcome measures of adenoma detection rate and withdrawal time. We performed a single center cohort study including patients aged ≥50 years undergoing screening colonoscopy during a 4.5 year period. Using multivariate regression, we measured the impact of delays on adenoma detection rate and withdrawal time, adjusting for age, gender, endoscopist, time of day of the procedure, and bowel preparation quality. Of 7905 screening colonoscopies, 2503 (32%) were delayed by >1 h. On multivariable analysis, cases delayed 1–2 h were associated with a significant decrease in adenoma detection rate relative to cases delayed ≤1 h (OR 0.88, 95% CI 0.78–1.00, p = 0.049). Withdrawal time was not significantly associated with case delays. Prolonged case delays over 1 h are associated with reduced adenoma detection rates. Future research on factors underlying prolonged delays may help mitigate these barriers to care and improve quality outcomes. [ABSTRACT FROM AUTHOR]

Individuals with germline pathogenic CDH1 variants have a high risk of hereditary diffuse gastric cancer. The sensitivity of EGD in detecting signet ring cell carcinoma (SRCC) in this population is low. We aimed to identify endoscopic findings and biopsy practices associated with detection of SRCC. This retrospective cohort included individuals with a germline pathogenic/likely pathogenic CDH1 variant undergoing at least 1 EGD at Memorial Sloan Kettering Cancer Center between January 1, 2006, and March 25, 2022. The primary outcome was detection of SRCC on EGD. Findings on gastrectomy were also assessed. The study included periods before and after implementation of the Cambridge protocol for endoscopic surveillance, allowing for assessment of a spectrum of biopsy practices. Ninety-eight CDH1 patients underwent at least 1 EGD at our institution. SRCC was detected in 20 (20%) individuals on EGD overall and in 50 (86%) of the 58 patients undergoing gastrectomy. Most SRCC foci were detected in the gastric cardia/fundus (EGD, 50%; gastrectomy, 62%) and body/transition zone (EGD, 60%; gastrectomy, 62%). Biopsy results of gastric pale mucosal areas were associated with detection of SRCC (P <.01). The total number of biopsy samples taken on EGD was associated with increased detection of SRCC (P =.01), with 43% detected when ≥40 samples were taken. Targeted biopsy sampling of gastric pale mucosal areas and increasing number of biopsy samples taken on EGD were associated with detection of SRCC. SRCC foci were mostly detected in the proximal stomach, supporting updated endoscopic surveillance guidelines. Further studies are needed to refine endoscopic protocols to improve SRCC detection in this high-risk population. [Display omitted] [ABSTRACT FROM AUTHOR]

Background Patients with celiac disease (CD) often have articular complaints, and small prior studies suggest an association with Ehlers-Danlos syndrome (EDS)/joint hypermobility syndrome (JHS). Aims This study examines the risks of EDS/JHS in patients with CD. Methods This cohort study compared all individuals in Sweden diagnosed with CD based on small intestinal biopsy between 1969–2008 ( n = 28,631) to 139,832 matched reference individuals, and to a second reference group undergoing biopsy without having CD ( n = 16,104). Rates of EDS/JHS were determined based on diagnostic codes in the Swedish Patient Register. Hazard ratios (HRs) for EDS/JHS were estimated through Cox regression. Results There are 45 and 148 cases of EDS/JHS in patients with CD and reference individuals, respectively. This corresponds to a 49% increased risk of EDS/JHS in CD (95%CI = 1.07–2.07). The HR for EDS was 2.43 (95%CI = 1.20–4.91) and for JHS 1.34 (95%CI = 0.93–1.95). Compared to reference individuals undergoing intestinal biopsy, CD was not a risk factor for EDS/JHS. A stronger association was seen in patients initially diagnosed with EDS/JHS and subsequently diagnosed with CD (odds ratio = 2.29; 95%CI = 1.21–4.34). Conclusions Individuals with CD have higher risk of EDS/JHS than the general population, which may be due to surveillance bias or factors intrinsic to celiac development. [ABSTRACT FROM AUTHOR]

Lynch syndrome is associated with pathogenic variants in 4 mismatch repair (MMR) genes that increase lifetime risk of colorectal cancer. Guidelines recommend intensive colorectal cancer surveillance with colonoscopy every 1–2 years starting at age 25 years for all carriers of Lynch syndrome–associated variants, regardless of gene product. We constructed a simulation model to analyze the effects of different ages of colonoscopy initiation and surveillance intervals for each MMR gene (MLH1 , MSH2 , MSH6 , and PMS2) on colorectal cancer incidence and mortality, quality-adjusted life-years, and cost. Using published literature, we developed a Markov simulation model of Lynch syndrome progression for patients with each MMR variant. The model simulated clinical trials of Lynch syndrome carriers, varying age of colonoscopy initiation (5-year increments from 25–40 years), and surveillance intervals (1–5 years). We assessed the optimal strategy for each gene, defined as the strategy with the highest quality-adjusted life-years and incremental cost-effectiveness ratio below a $100,000 willingness-to-pay threshold. Optimal surveillance for patients with pathogenic variants in the MLH1 and MSH2 genes was colonoscopy starting at age 25 years, with 1- to 2-year surveillance intervals. Initiating colonoscopy at age 35 and 40 years, with 3-year intervals, was cost-effective for patients with pathogenic variants in MSH6 or PMS2 , respectively. We developed a simulation model to select optimal surveillance starting ages and intervals for patients with Lynch syndrome based on MMR variant. The model supports recommendations for intensive surveillance of patients with Lynch syndrome–associated variants in MLH1 or MSH2. However, for patients with Lynch syndrome–associated variants of MSH6 or PMS2 , later initiation of surveillance at 35 and 40 years, respectively, and at 3-year intervals, can be considered. This study analyzed data on risk of colorectal cancer in patients with Lynch syndrome and found that risk varies with genetic alteration associated with the disease, which should be used to determine starting age for colonoscopy surveillance and interval. [ABSTRACT FROM AUTHOR]

Our understanding of outcomes and disease time course of COVID-19 in patients with gastrointestinal (GI) symptoms remains limited. In this study we characterize the disease course and severity of COVID-19 among hospitalized patients with gastrointestinal manifestations in a large, diverse cohort from the Unites States. This retrospective study evaluated hospitalized individuals with COVID-19 between March 11 and April 28, 2020 at two affiliated hospitals in New York City. We evaluated the association between GI symptoms and death, and also explored disease duration, from symptom onset to death or discharge. Of 2804 patients hospitalized with COVID-19, the 1,084 (38.7%) patients with GI symptoms were younger (aOR for age ≥75, 0.59; 95% CI, 0.45-0.77) and had more co-morbidities (aOR for modified Charlson comorbidity score ≥2, 1.22; 95% CI, 1.01-1.48) compared to those without GI symptoms. Individuals with GI symptoms had better outcomes, with a lower likelihood of intubation (aHR, 0.66; 95% CI, 0.55-0.79) and death (aHR, 0.71; 95% CI, 0.59-0.87), after adjusting for clinical factors. These patients had a longer median disease course from symptom onset to discharge (13.8 vs 10.8 days, log-rank p =.048; among 769 survivors with available symptom onset time), which was driven by longer time from symptom onset to hospitalization (7.4 vs 5.4 days, log-rank P <.01). Hospitalized patients with GI manifestations of COVID-19 have a reduced risk of intubation and death, but may have a longer overall disease course driven by duration of symptoms prior to hospitalization. [ABSTRACT FROM AUTHOR]

Carriers of pathogenic variants in CDH1 have a high risk of hereditary diffuse gastric cancer (HDGC). Guidelines recommend prophylactic total gastrectomy (PTG) at age 20–30 years, although there is controversy over the optimal age. We developed a simulation model to analyze the effects of PTG at different ages on quality-adjusted life-years (QALYs), cancer mortality, and life expectancy. We used a Markov model of HDGC progression associated with pathogenic variants in CDH1 to simulate outcomes of hypothetical cohorts with different ages at time of PTG (ages 20–79 years). Model inputs including health state transition probabilities, mortality and complication rates, quality of life utility values, and endoscopic surveillance sensitivity were derived from publications. The primary outcome, used to determine the optimal strategy, was age at which PTG yielded the highest QALYs. Secondary outcomes were cancer mortality and unadjusted life-years. Our model found that for men, the optimal age for PTG is 39 years, resulting in 32.01 incremental QALYs, 58.81 life-years (biologic age, 72.81 years), and lifetime cancer mortality of 8.5%. Incorporating endoscopic surveillance prior to PTG decreased cancer mortality to 6.7%, but had lower QALYs (31.59). PTG at age 30 reduced cancer mortality to 3.2%, with 31.45 incremental QALYs. For women, the optimal age for PTG was calculated to be 30 years, with 33.09 incremental QALYs, 66.17 life-years (biologic age, 80.17 years), and lifetime cancer mortality of 1.6%. Addition of endoscopic surveillance did not decrease the risk of HDGC mortality in women. Using a Markov model of HDGC progression associated with pathogenic variants in CDH1 to simulate outcomes, we found the optimal ages for PTG to be 39 years for men and 30 years for women, when QALYs are the primary endpoint. These ages for PTG are older than those of current recommendations. [ABSTRACT FROM AUTHOR]

Background & Aims Anemia is common in patients with celiac disease (CD) and a frequent mode of presentation. Guidelines recommend screening patients with iron-deficiency anemia (IDA) for CD. However, the reported prevalence of CD in patients with IDA varies. We performed a systematic review to determine the prevalence of biopsy-verified CD in patients with IDA. Methods We performed a systematic review of articles published in PubMed Medline or EMBASE through July 2017 for the term “celiac disease” combined with “anemia” or “iron deficiency.” We used fixed-effects inverse variance-weighted models to measure the pooled prevalence of CD. Meta-regression was used to assess subgroup heterogeneity. Results We identified 18 studies composed of 2998 patients with IDA for inclusion in our analysis. Studies originated from the United Kingdom, United States, Italy, Turkey, Iran, and Israel. The crude unweighted prevalence of CD was 4.8% (n = 143). Using a weighted pooled analysis, we found a prevalence of biopsy-confirmed CD of 3.2% (95% confidence interval = 2.6-3.9) in patients with IDA. However, heterogeneity was high (I 2 = 67.7%). The prevalence of CD was not significantly higher in studies with a mean participant age older or younger than 18 years or in studies with a mixed-sex vs female-predominant (≥60%) population. On meta-regression, year of publication, female proportion, age at CD testing, and prevalence in the general population were not associated with the prevalence of CD in patients with IDA. In the 8 studies fulfilling all our quality criteria, the pooled prevalence of CD was 5.5% (95% confidence interval = 4.1–6.9). Conclusions In a systematic review and meta-analysis, we found that approximately 1 in 31 patients with IDA have histologic evidence of CD. This prevalence value justifies the practice of testing patients with IDA for CD. [ABSTRACT FROM AUTHOR]