Bleeding due to primary or metastatic gastrointestinal (GI) tumors remains clinically challenging. Bleeding is further complicated in the setting of underlying friable neovascularization of tumors and coagulopathy. Endoscopic hemostatic therapeutic options have traditionally involved the use of thermal/mechanical therapy in conjunction with injection therapy. This review looks at the role of endoscopy in managing tumor-related GI bleeding, specifically contact and non-contact thermal therapy, radiofrequency ablation, endoloops, epinephrine and ethanol injection, and, most recently, Hemospray. Overall, current data show that endoscopic therapy is limited, with high rebleeding rates and a failure to improve overall outcomes. Larger clinical trials are needed to determine the efficacy of current techniques and establish therapeutic algorithms, with the goal of achieving primary hemostasis and reducing rebleeding rates.

Background: Mast syndrome, an autosomal recessive, progressive form of hereditary spastic paraplegia, is associated with mutations in SPG21 loci that encode maspardin protein. Although SPG21^-/- mice exhibit lower limb dysfunction, the role of maspardin loss in mast syndrome is unclear. Objective: To test the hypothesis that loss of maspardin attenuates the growth and maturation of cortical neurons in SPG21^-/- mice. Methods and Results: In a randomized experimental design SPG21^-/- mice demonstrated significantly less agility and coordination compared to wild-type mice in beam walk, ledge, and hind limb clasp tests for assessing neuronal dysfunction (p ≤ 0.05). The SPG21^-/- mice exhibited symptoms of mast syndrome at 6 months which worsened in 12-month-old cohort, suggesting progressive dysfunction of motor neurons. Ex vivo, wild-type cortical neurons formed synapses, ganglia and aggregates at 96 h, whereas SPG21^-/- neurons exhibited attenuated growth with markedly less axonal branches. Additionally, epidermal growth factor markedly promoted the growth and maturation of SPG21^+/+ cortical neurons but not SPG21^-/- neurons. Consequently, quantitative RT-PCR identified a significant reduction in the expression of a subset of EGF-EGFR signaling targets. Conclusions: Our current study uncovered a direct role for maspardin in normal and EGF-induced growth and maturation of primary cortical neurons. The loss of maspardin resulted in attenuated growth, axonal branching, and attenuation of EGF signaling. Reinstating the functions of maspardin may reverse hind limb impairment associated with neuronal dysfunction in mast syndrome patients.

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