Esophageal regeneration following surgical implantation of a tissue engineered esophageal implant in a pediatric model

Diseases of the esophagus, damage of the esophagus due to injury or congenital defects during fetal esophageal development, i.e., esophageal atresia (EA), typically require surgical intervention to restore esophageal continuity. The development of tissue engineered tubular structures would improve the treatment options for these conditions by providing an alternative that is organ sparing and can be manufactured to fit the exact dimensions of the defect. An autologous tissue engineered Cellspan Esophageal ImplantTM (CEI) was surgically implanted into piglets that underwent surgical resection of the esophagus. Multiple survival time points, post-implantation, were analyzed histologically to understand the tissue architecture and time course of the regeneration process. In addition, we investigated CT imaging as an “in-life” monitoring protocol to assess tissue regeneration. We also utilized a clinically relevant animal management paradigm that was essential for long term survival. Following implantation, CT imaging revealed early tissue deposition and the formation of a contiguous tissue conduit. Endoscopic evaluation at multiple time points revealed complete epithelialization of the lumenal surface by day 90. Histologic evaluation at several necropsy time points, post-implantation, determined the time course of tissue regeneration and demonstrated that the tissue continues to remodel over the course of a 1-year survival time period, resulting in the development of esophageal structural features, including the mucosal epithelium, muscularis mucosae, lamina propria, as well as smooth muscle proliferation/migration initiating the formation of a laminated adventitia. Long term survival (1 year) demonstrated restoration of oral nutrition, normal animal growth and the overall safety of this treatment regimen.

Association of State Medicaid Income Eligibility Limits and Long-Term Survival After Cancer Diagnosis in the United States

PURPOSE: To examine the association between historic state Medicaid income eligibility limits and long-term survival among patients with cancer. METHODS: 1,449,144 adults age 18-64 years newly diagnosed with 19 common cancers between 2010 and 2013 were identified from the National Cancer Database. States' Medicaid income eligibility limits were categorized as ≤ 50%, 51%-137%, and ≥ 138% of federal poverty level (FPL). Survival time was measured from diagnosis date through December 31, 2017, for up to an 8-year follow-up. Multivariable Cox proportional hazards models with age as time scale were used to assess associations of eligibility limits and stage-specific survival, adjusting for the effects of sex, metropolitan statistical area, comorbidities, year of diagnosis, facility type and volume, and state. RESULTS: Among patients with newly diagnosed cancer age 18-64 years, patients living in states with lower Medicaid income eligibility limits had worse survival for most cancers in both early and late stages, compared with those living in states with Medicaid income eligibility limits ≥ 138% FPL. A dose-response relationship was observed for most cancers with lower income limits associated with worse survival (13 of 17 cancers evaluated for early-stage cancers, and 11 of 17 cancers evaluated for late-stage cancers, and leukemia and brain tumors with P-trend < .05). CONCLUSION: Lower Medicaid income eligibility limits were associated with worse long-term survival within stage; increasing Medicaid income eligibility may improve survival after cancer diagnosis.