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Personalized risk assessment for dynamic transition of gastric neoplasms.

ABSTRACT: BACKGROUND:To develop an individually-tailored dynamic risk assessment model following a multistep, multifactorial process of the Correa's gastric cancer model. METHODS:First, we estimated the state-to-state transition rates following Correa's five-step carcinogenic model and assessed the effect of risk factors, including Helicobacter pylori infection, history of upper gastrointestinal disease, lifestyle, and dietary habits, on the step-by-step transition rates using data from a high-risk population in Matsu Islands, Taiwan. Second, we incorporated information on the gastric cancer carcinogenesis affected by genomic risk factors (including inherited susceptibility and irreversible genomic changes) based on literature to generate a genetic and epigenetic risk assessment model by using a simulated cohort identical to the Matsu population. The combination of conventional and genomic risk factors enables us to develop the personalized transition risk scores and composite scores. RESULTS:The state-by-state transition rates per year were 0.0053, 0.7523, 0.1750, and 0.0121 per year from normal mucosa to chronic active gastritis, chronic active gastritis to atrophic gastritis, atrophic gastritis to intestinal metaplasia, and intestinal metaplasia to gastric cancer, respectively. Compared with the median risk group, the most risky decile had a 5.22-fold risk of developing gastric cancer, and the least risky decile around one-twelfth of the risk. The median 10-year risk for gastric cancer incidence was 0.77%. The median lifetime risk for gastric cancer incidence was 5.43%. By decile, the 10-year risk ranged from 0.06 to 4.04% and the lifetime risk ranged from 0.42 to 21.04%. CONCLUSIONS:We demonstrate how to develop a personalized dynamic risk assessment model with the underpinning of Correa's cascade to stratify the population according to their risk for progression to gastric cancer. Such a risk assessment model not only facilitates the development of an individually-tailored preventive strategy with treatment for H. pylori infection and endoscopic screening but also provides short-term and long-term indicators to evaluate the program effectiveness.

SUBMITTER: Fann JC

PROVIDER: S-EPMC6245882 | biostudies-other | 2018 Nov

REPOSITORIES: biostudies-other

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Personalized risk assessment for dynamic transition of gastric neoplasms.

Fann Jean Ching-Yuan JC Chiang Tsung-Hsien TH Yen Amy Ming-Fang AM Lee Yi-Chia YC Wu Ming-Shiang MS Chen Hsiu-Hsi HH

Journal of biomedical science 20181119 1

<h4>Background</h4>To develop an individually-tailored dynamic risk assessment model following a multistep, multifactorial process of the Correa's gastric cancer model.<h4>Methods</h4>First, we estimated the state-to-state transition rates following Correa's five-step carcinogenic model and assessed the effect of risk factors, including Helicobacter pylori infection, history of upper gastrointestinal disease, lifestyle, and dietary habits, on the step-by-step transition rates using data from a h ...[more]

PMID: 30453970

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Project description:ImportanceEsophagogastroduodenoscopy (EGD) is a common procedure used to examine upper gastrointestinal diseases. Although cimetropium bromide and other antispasmodic agents are commonly administered as premedication to inhibit peristalsis during EGD examination, there are few data regarding the benefits of cimetropium bromide for the detection of gastric neoplasms.ObjectiveTo investigate the association between the use of cimetropium bromide as premedication and gastric neoplasm detection rates during EGD examination.Design, setting, and participantsThis propensity score-matched retrospective cohort study included 67 683 participants who received EGD screening at the Health Promotion Center of Seoul St. Mary's Hospital, The Catholic University of Korea, from January 2, 2010, to June 30, 2017. Data were analyzed from April 1 to December 30, 2021.ExposuresParticipants were divided into 2 groups: those who received cimetropium bromide before EGD examination (intervention group) and those who did not (control group).Main outcomes and measuresGastric neoplasm detection rates.ResultsAmong 67 683 participants, the mean (SD) age was 48.6 (10.8) years, and 36 517 participants (54.0%) were male; all participants were Asian (a racially homogenous population). Of those, 28 280 participants (41.8%; mean [SD] age, 50.3 [10.6] years; 57.8% male) received cimetropium bromide, and 39 403 participants (58.2%; mean [SD] age, 47.4 [10.8] years; 51.2% male) did not. Propensity score matching based on confounding variables yielded 41 670 matched participants (20 835 pairs). Detected lesions included 52 dysplasias (0.12%), 40 early cancers (0.10%), 7 advanced cancers (0.02%), and 3 lymphomas (0.01%). Gastric neoplasm detection rates were significantly higher in the intervention group (63 participants [0.30%]) vs the control group (39 participants [0.19%]; P = .02). A significant difference in the combined detection rate of dysplasia and early gastric cancer was found between those in the intervention group (57 participants [0.27%]) vs the control group (35 participants [0.17%]; P = .02). For small gastric lesions (<1 cm), those who received cimetropium bromide had higher detection rates (24 participants [0.12%]) than those who did not (11 participants [0.05%]; P = .03). Lesions in the gastric body were detected significantly more often in the intervention group (34 participants [0.16%]) vs the control group (15 participants [0.07%]; P = .007). In multivariate analyses involving all 67 683 participants, the use of cimetropium bromide was more likely to detect gastric neoplasms compared with nonuse (odds ratio, 1.42; 95% CI, 1.04-1.95; P = .03).Conclusions and relevanceIn this study, the use of cimetropium bromide as premedication was significantly associated with increased gastric neoplasm detection rates during EGD screening, and lesions in the gastric body were detected more frequently among those who received cimetropium bromide compared with those who did not. These findings suggest that cimetropium bromide may be considered as premedication before EGD examination among individuals with no contraindications.

Project description:BackgroundMyeloproliferative neoplasms, such as polycythemia vera, essential thrombocythemia, and myelofibrosis, are chronic hematologic cancers with varied progression rates. The genomic characterization of patients with myeloproliferative neoplasms offers the potential for personalized diagnosis, risk stratification, and treatment.MethodsWe sequenced coding exons from 69 myeloid cancer genes in patients with myeloproliferative neoplasms, comprehensively annotating driver mutations and copy-number changes. We developed a genomic classification for myeloproliferative neoplasms and multistage prognostic models for predicting outcomes in individual patients. Classification and prognostic models were validated in an external cohort.ResultsA total of 2035 patients were included in the analysis. A total of 33 genes had driver mutations in at least 5 patients, with mutations in JAK2, CALR, or MPL being the sole abnormality in 45% of the patients. The numbers of driver mutations increased with age and advanced disease. Driver mutations, germline polymorphisms, and demographic variables independently predicted whether patients received a diagnosis of essential thrombocythemia as compared with polycythemia vera or a diagnosis of chronic-phase disease as compared with myelofibrosis. We defined eight genomic subgroups that showed distinct clinical phenotypes, including blood counts, risk of leukemic transformation, and event-free survival. Integrating 63 clinical and genomic variables, we created prognostic models capable of generating personally tailored predictions of clinical outcomes in patients with chronic-phase myeloproliferative neoplasms and myelofibrosis. The predicted and observed outcomes correlated well in internal cross-validation of a training cohort and in an independent external cohort. Even within individual categories of existing prognostic schemas, our models substantially improved predictive accuracy.ConclusionsComprehensive genomic characterization identified distinct genetic subgroups and provided a classification of myeloproliferative neoplasms on the basis of causal biologic mechanisms. Integration of genomic data with clinical variables enabled the personalized predictions of patients' outcomes and may support the treatment of patients with myeloproliferative neoplasms. (Funded by the Wellcome Trust and others.).

Project description:RationaleCardiorespiratory insufficiency (CRI) is a term applied to the manifestations of loss of normal cardiorespiratory reserve and portends a bad outcome. CRI occurs commonly in hospitalized patients, but its risk escalation patterns are unexplored.ObjectivesTo describe the dynamic and personal character of CRI risk evolution observed through continuous vital sign monitoring of individual step-down unit patients.MethodsUsing a machine learning model, we estimated risk trends for CRI (defined as exceedance of vital sign stability thresholds) for each of 1,971 admissions (1,880 unique patients) to a 24-bed adult surgical trauma step-down unit at an urban teaching hospital in Pittsburgh, Pennsylvania using continuously recorded vital signs from standard bedside monitors. We compared and contrasted risk trends during initial 4-hour periods after step-down unit admission, and again during the 4 hours immediately before the CRI event, between cases (ever had a CRI) and control subjects (never had a CRI). We further explored heterogeneity of risk escalation patterns during the 4 hours before CRI among cases, comparing personalized to nonpersonalized risk.Measurements and main resultsEstimated risk was significantly higher for cases (918) than control subjects (1,053; P ≤ 0.001) during the initial 4-hour stable periods. Among cases, the aggregated nonpersonalized risk trend increased 2 hours before the CRI, whereas the personalized risk trend became significantly different from control subjects 90 minutes ahead. We further discovered several unique phenotypes of risk escalation patterns among cases for nonpersonalized (14.6% persistently high risk, 18.6% early onset, 66.8% late onset) and personalized risk (7.7% persistently high risk, 8.9% early onset, 83.4% late onset).ConclusionsInsights from this proof-of-concept analysis may guide design of dynamic and personalized monitoring systems that predict CRI, taking into account the triage and real-time monitoring utility of vital signs. These monitoring systems may prove useful in the dynamic allocation of technological and clinical personnel resources in acute care hospitals.

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Personalized risk assessment for dynamic transition of gastric neoplasms.

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Personalized risk assessment for dynamic transition of gastric neoplasms.

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