Bone metastatic disease: taking aim at new therapeutic targets.

Conventional treatment for metastatic bone pain requires a multidisciplinary approach (medical therapy, surgery, and radiation), but is primarily palliative. Biphosphonates introduced the concept of disease-modifying therapy, by effectively reducing bone pain and skeletal related events in patients suffering from bone metastatic cancer. In the past decade, the growing knowledge of bone biology and our understanding of the molecular mechanisms at the basis of the interaction between cancer cells and bone matrix led to the identification of new therapeutic targets for innovative "smart drugs". The most investigated is the RANK/RANKL/OPG pathway, and denosumab, among novel targeted therapies, is the molecule that is in the most advanced development phase. Additional targets have been identified and potential novel therapeutic interventions, classified as inhibitors of bone resorption or stimulators of bone formation, are under preclinical and clinical evaluation. These promising targets include cathepsin K, the Src tyrosine kinases, integrins, chloride channels, the parathyroid hormone-related peptide, endotelin-1, sclerostin, and TGF-beta. Other pathways or molecules expressed by bone cells and cancer cells, such as CXCR4, GPNMB, EGF-family ligands, Wnt/DKK1, and MIP-1 alpha have recently emerged as potential targets. The aim of this review is to discuss the molecular mechanisms behind these emerging therapeutic targets in bone metastases and to give an overview of results from those in advanced clinical phases.

Determinants of patient satisfaction in postoperative pain management following hand ambulatory day-surgery.

AIM: Adequate postoperative analgesia is a prerequisite for successful ambulatory surgery and continues to be a challenge for anesthesiologists. The goal of the study was to analyze what are determinants of patients' overall satisfaction in postoperative pain management after ambulatory hand surgery. METHODS: Patients undergoing ambulatory hand surgery received oral fixed association tramadol/acetaminophen 37.5/325 mg every 6 hours during the first 48 hours after operation. Analgesic efficacy was evaluated by self-assessment of pain intensity by numeric rating scale. Patients also recorded total number of daily study analgesic tablets, frequency and severity of adverse events, sleep pain interference (SPI 0-10), number of rescue doses and patient global assessment (PGA) on a 4-grade scale. Success ratings on the PGA were considered "good" and "excellent". Preoperative pain intensity, analgesic use, and expectation were also recorded. RESULTS: One hundred and forty-three subjects were evaluated in the study. The percentage of patients who reported rating of success on the PGA was 88.8%. The most significant determinant of failure on the PGA was the presence of moderate to severe adverse events (R=-0.85). Determinants of ratings of success on PGA were adequate analgesia and SPI ≤ 4. Predictors of successful patient satisfaction were preoperative pain ≤ 4 on NRS, lack of preoperative analgesic consumption, expected pain >6 on NRS, and lower education level. Weak correlation (R=0.26) was observed between mean daily pain intensity and analgesics intake. CONCLUSION: Results indicate that the oral association tramadol/acetaminophen 37,5/325 mg is effective for the management of postoperative pain after ambulatory hand surgery. The lack of adverse events is the most important determinant of patient satisfaction, followed by the analgesic efficacy.