Characterization andManagement of Hedgehog Pathway Inhibitor-Related Adverse Events in Patients With Advanced BasalCell Carcinoma

International audienceAbnormal activation of hedgehog pathway signaling is a key driver in the pathogenesis of basal cell carcinoma (BCC). Vismodegib, a first-in-class small-molecule inhibitor of hedgehog pathway signaling, is approved by regulatory authorities for the treatment of adults who have metastatic BCC or locally advanced BCC that has recurred after surgery, or who are notcandidates for surgery and who are not candidates for radiation. A second inhibitor, sonidegib, was also recently approved for the same patient group with locally advanced BCC. Adverse events (AEs) commonly observed in hedgehog pathway inhibitor (HPI)-treated patients include muscle spasms, ageusia/dysgeusia, alopecia, weight loss, and asthenia (fatigue).These AEs are thought to bemechanistically related to inhibition of the hedgehog pathway in normal tissue. Although the severity of the majority of AEs associated with HPIs is grade 1–2, the long-termnature of these AEs can lead to decreased quality of life, treatment interruption, and in some cases discontinuation, all of which might affect clinical outcome.The incidence, clinical presentation, putative mechanisms, and management strategies for AEs related to HPIs in advanced BCC are described. These observations represent the first step toward the development of mechanism-based preventive and management strategies.Knowledge of these AEs will allow health care professionals to provide appropriate counseling and supportive care interventions, all of which will contribute to improved quality of life and optimal benefit from therapy

Diagnosis and conservative management of degenerative lumbar spondylolisthesis

Degenerative spondylolisthesis (DS) is a disorder that causes the slip of one vertebral body over the one below due to degenerative changes in the spine. Lumbar DS is a major cause of spinal canal stenosis and is often related to low back and leg pain. We reviewed the symptoms, prognosis and conservative treatments for symptoms associated with DS. PubMed and MEDLINE databases (1950–2007) were searched for the key words “spondylolisthesis”, “pseudospondylolisthesis”, “degenerative spondylolisthesis”, “spinal stenosis”, “lumbar spine”, “antherolisthesis”, “posterolisthesis”, “low back pain”, and “lumbar instability”. All relevant articles in English were reviewed. Pertinent secondary references were also retrieved. The prognosis of patients with DS is favorable, however, those who suffer from neurological symptoms such as intermittent claudication or vesicorectal disorder, will most probably experience neurological deterioration if they are not operated upon. Nonoperative treatment should be the initial course of action in most cases of DS, with or without neurologic symptoms. Treatment options include use of analgesics and NSAIDs to control pain; epidural steroid injections, and physical methods such as bracing and flexion strengthening exercises. An up-to-date knowledge on diagnosis and prevention of lumbar DS can assist in determination of future research goals. Additional studies are required to establish treatment protocols for the conservative treatment of DS