Are there specific endosonographic features in Crohn's patients with perianal fistulae?

Both 2-dimensional and 3-dimensional endoanal ultrasounds have been shown to be accurate in the definition of the anatomy of complex fistulae-in-ano in patients with perianal Crohn's disease. Recently, a Crohn's Ultrasound Fistula Sign (CUFS) has been suggested as a discriminating feature of perianal Crohn's disease as has the presence of fistulous debris and fistular bifurcation. We blindly assessed 197 patients (39 Crohn's fistulae and 158 cryptogenic fistulae) to determine if these signs differentiated fistula types. The incidence of CUFS in Crohn's cases was 17/39 (43.6%) and in cryptogenic cases was 4/158 (2.5%) (P<0.0001). The sensitivity, specificity, positive and negative predictive values and accuracy for CUFS were 43.6%, 97.5%, 80.9%, 87.5% and 86.8%, respectively. The presence of debris and fistula bifurcation in evaluable cases had a high specificity (87.2% and 81.8%, respectively) but poor sensitivity. The kappa values for or against CUFS, debris and bifurcation in Crohn's cases between 2 observers blinded to the diagnosis were 0.85, 0.72 and 0.93, respectively and in cryptogenic fistulae were 0.89, 0.85 and 0.80, respectively. The kappa values of an agreed consensus for CUFS in Crohn's disease, cryptogenic fistulae and overall with a third observer with no ultrasound experience were 0.62, 0.85 and 0.77, respectively. The presence of CUFS differentiates Crohn's-related from cryptogenic fistulae-in-ano with a high level of agreement for this sign between experienced and inexperienced observers blinded to the underlying diagnosis.

Caspase-mediated cleavage converts Livin from an antiapoptotic to a proapoptotic factor: implications for drug-resistant melanoma.

Inhibitor of apoptosis protein (IAP) is a family of intracellular proteins that plays an essential role in the regulation of apoptosis. Recently, we and others discovered a new member of this family, termed Livin. Many studies have focused on the inhibitory effect of IAPs on caspases. Here, we describe a novel regulatory mechanism by which Livin is cleaved by the caspases. Strikingly, the cleaved Livin, although containing intact baculovirus IAP repeat and RING domains, does not only lose its antiapoptotic function but also gains a proapoptotic effect. The cleavage is site specific at Asp-52 and is restricted to effector caspase-3 and -7. Most importantly, we demonstrate the role of Livin and this regulatory mechanism in the drug resistance of melanoma patients. Using primary cultures derived from melanoma patients, we found a correlation between Livin overexpression, in vitro drug resistance, and the patient's clinical response.