Survival Outcomes for Malignant Peritoneal Mesothelioma at Academic Versus Community Hospitals.

BACKGROUND: Malignant peritoneal mesothelioma is a rare disease with poor outcomes. Cytoreductive surgery with hyperthermic intraperitoneal chemotherapy is the cornerstone of therapy. We aim to compare outcomes of malignant peritoneal mesothelioma treated at academic versus community hospitals. METHODS: This was a retrospective cohort study using the National Cancer Database to identify patients with malignant peritoneal mesothelioma from 2004 to 2016. Patients were divided according to treating facility type: academic or community. Outcomes were assessed using log-rank tests, Cox proportional-hazard modeling, and Kaplan-Meier survival statistics. RESULTS: In total, 2682 patients with malignant peritoneal mesothelioma were identified. A total of 1272 (47.4%) were treated at an academic facility and 1410 (52.6%) were treated at a community facility. Five hundred forty-six (42.9%) of patients at academic facilities underwent debulking or radical surgery compared to 286 (20.2%) at community facilities. Three hundred sixty-six (28.8%) of patients at academic facilities received chemotherapy on the same day as surgery compared to 147 (10.4%) of patients at community facilities. Unadjusted 5-year survival was 29.7% (95% CI 26.7-32.7) for academic centers compared to 18.3% (95% CI 16.0-20.7) for community centers. In multivariable analysis, community facility was an independent predictor of increased risk of death (HR: 1.19, 95% CI 1.08-1.32, p = 0.001). CONCLUSIONS: We demonstrate better survival outcomes for malignant peritoneal mesothelioma treated at academic compared to community facilities. Patients at academic centers underwent surgery and received chemotherapy on the same day as surgery more frequently than those at community centers, suggesting that malignant peritoneal mesothelioma patients may be better served at experienced academic centers.

MYC gene delivery to adult mouse utricles stimulates proliferation of postmitotic supporting cells in vitro.

The inner ears of adult humans and other mammals possess a limited capacity for regenerating sensory hair cells, which can lead to permanent auditory and vestibular deficits. During development and regeneration, undifferentiated supporting cells within inner ear sensory epithelia can self-renew and give rise to new hair cells; however, these otic progenitors become depleted postnatally. Therefore, reprogramming differentiated supporting cells into otic progenitors is a potential strategy for restoring regenerative potential to the ear. Transient expression of the induced pluripotency transcription factors, Oct3/4, Klf4, Sox2, and c-Myc reprograms fibroblasts into neural progenitors under neural-promoting culture conditions, so as a first step, we explored whether ectopic expression of these factors can reverse supporting cell quiescence in whole organ cultures of adult mouse utricles. Co-infection of utricles with adenoviral vectors separately encoding Oct3/4, Klf4, Sox2, and the degradation-resistant T58A mutant of c-Myc (c-MycT58A) triggered significant levels of supporting cell S-phase entry as assessed by continuous BrdU labeling. Of the four factors, c-MycT58A alone was both necessary and sufficient for the proliferative response. The number of BrdU-labeled cells plateaued between 5-7 days after infection, and then decreased ~60% by 3 weeks, as many cycling cells appeared to enter apoptosis. Switching to differentiation-promoting culture medium at 5 days after ectopic expression of c-MycT58A temporarily attenuated the loss of BrdU-labeled cells and accompanied a very modest but significant expansion of the sensory epithelium. A small number of the proliferating cells in these cultures labeled for the hair cell marker, myosin VIIA, suggesting they had begun differentiating towards a hair cell fate. The results indicate that ectopic expression of c-MycT58A in combination with methods for promoting cell survival and differentiation may restore regenerative potential to supporting cells within the adult mammalian inner ear.

Bilayered constructs aimed at osteochondral strategies: the influence of medium supplements in the osteogenic and chondrogenic differentiation of amniotic fluid-derived stem cells.

The development of osteochondral tissue engineered interfaces would be a novel treatment for traumatic injuries and aging associated diseases that affect joints. This study reports the development of a bilayered scaffold, which consists of both bone and cartilage regions. On the other hand, amniotic fluid-derived stem cells (AFSCs) could be differentiated into either osteogenic or chondrogenic cells, respectively. In this study we have developed a bilayered scaffolding system, which includes a starch/polycaprolactone (SPCL) scaffold for osteogenesis and an agarose hydrogel for chondrogenesis. AFSC-seeded scaffolds were cultured for 1 or 2 weeks in an osteochondral-defined culture medium containing both osteogenic and chondrogenic differentiation factors. Additionally, the effect of the presence or absence of insulin-like growth factor-1 (IGF-1) in the culture medium was assessed. Cell viability and phenotypic expression were assessed within the constructs in order to determine the influence of the osteochondral differentiation medium. The results indicated that, after osteogenic differentiation, AFSCs that had been seeded onto SPCL scaffolds did not require osteochondral medium to maintain their phenotype, and they produced a protein-rich, mineralized extracellular matrix (ECM) for up to 2 weeks. However, AFSCs differentiated into chondrocyte-like cells appeared to require osteochondral medium, but not IGF-1, to synthesize ECM proteins and maintain the chondrogenic phenotype. Thus, although IGF-1 was not essential for creating osteochondral constructs with AFSCs in this study, the osteochondral supplements used appear to be important to generate cartilage in long-term tissue engineering approaches for osteochondral interfaces. In addition, constructs generated from agarose-SPCL bilayered scaffolds containing pre-differentiated AFSCs may be useful for potential applications in regeneration strategies for damaged or diseased joints.