Biennial Endoscopic Surveillance of Gastrointestinal Metaplasia and Its Subtypes Reduces Gastric Cancer Mortality and Is Cost-Effective in a Markov State Transition Model.

OBJECTIVES: Gastric cancer in the United States has a low survival rate mainly because of the late stage of diagnosis. Furthermore, there are no well-established guidelines concerning screening and surveillance even for higher risk patients such as those with nondysplastic noncardia gastrointestinal metaplasia (GIM), and thus they are not routinely performed. This study was designed to provide new evidence-based data that can be used to support the implementation of biennial surveillance guidelines in individuals with nondysplastic noncardia GIM. This practice can help detect early malignant lesions, thereby decreasing morbidity and mortality. We evaluated the cost-effectiveness of surveillance endoscopies for noncardia gastric cancer in populations with two different pathological diagnoses: mixed GIM and incomplete GIM (iGIM). METHODS: Markov state transition models were developed using a cohort simulation of 1000 hypothetical patients. Analysis was conducted for both mixed and iGIM. Quality-adjusted life-years and transition probabilities were derived from the published medical literature. Costs associated with endoscopy, cancer care, and surgery were based on Medicare reimbursement. A willingness-to-pay threshold of $100,000 per quality-adjusted life-year was used to determine cost-effectiveness. RESULTS: Our study determined that it is significantly cost-effective to perform biennial endoscopy surveillance in patients who have been incidentally found to have noncardia mixed GIM, with a cost savings of $5783.84 per person, and in those with iGIM, with a cost savings of $8093.08 per person. CONCLUSIONS: Biennial endoscopy surveillance should be considered in all individuals found to have mixed or incomplete noncardia GIM on endoscopy. Furthermore, screening specifically for iGIM after differentiating between the two groups can lead to further cost savings. As such, we recommend that pathologists routinely differentiate between the two and recommend robust routine surveillance of iGIM.

Development of humanized mouse and rat models with full-thickness human skin and autologous immune cells.

The human skin is a significant barrier for protection against pathogen transmission. Rodent models used to investigate human-specific pathogens that target the skin are generated by introducing human skin grafts to immunocompromised rodent strains. Infection-induced immunopathogenesis has been separately studied in humanized rodent models developed with human lymphoid tissue and hematopoietic stem cell transplants. Successful co-engraftment of human skin, autologous lymphoid tissues, and autologous immune cells in a rodent model has not yet been achieved, though it could provide a means of studying the human immune response to infection in the human skin. Here, we introduce the human Skin and Immune System (hSIS)-humanized NOD-scid IL2Rγnull (NSG) mouse and Sprague-Dawley-Rag2tm2hera Il2rγtm1hera (SRG) rat models, co-engrafted with human full-thickness fetal skin, autologous fetal lymphoid tissues, and autologous fetal liver-derived hematopoietic stem cells. hSIS-humanized rodents demonstrate the development of human full-thickness skin, along with autologous lymphoid tissues, and autologous immune cells. These models also support human skin infection following intradermal inoculation with community-associated methicillin-resistant Staphylococcus aureus. The co-engraftment of these human skin and immune system components into a single humanized rodent model could provide a platform for studying human skin infections.