Cannabinoid levels description in a cohort of patients with chronic and neuropathic pain treated with Cannabis decoction: A possible role of TDM.

The phytocomplex of Cannabis is made up of approximately 500 substances: terpeno-phenols metabolites, including Δ-9-tetrahydrocannabinol and cannabidiol, exhibit pharmacological activity. Medical Cannabis has several pharmacological potential applications, in particular in the management of chronic and neuropathic pain. In the literature, a few data are available concerning cannabis pharmacokinetics, efficacy and safety. Thus, aim of the present study was the evaluation of cannabinoid pharmacokinetics in a cohort of patients, with chronic and neuropathic pain, treated with inhaled medical cannabis and decoction, as a galenic preparation. In this study, 67 patients were enrolled. Dried flower tops with different THC and CBD concentrations were used: Bedrocan® medical cannabis with THC level standardized at 19% and with a CBD level below 1%, Bediol® medical cannabis with THC and CBD level standardized at similar concentration of 6.5% and 8%, respectively. Cannabis was administered as a decoction in 47 patients and inhaled in 11 patients. The blood withdrawn was obtained before the new dose administration at the steady state and metabolites plasma concentrations were measured with an UHPLC-MS/MS method. Statistically significant differences were found in cannabinoids plasma exposure between inhaled and oral administration of medical cannabis, between male and female and cigarette smokers. For the first time, differences in cannabinoid metabolites exposures between different galenic formulations were suggested in patients. Therapeutic drug monitoring could be useful to allow for dose adjustment, but further studies in larger cohorts of patients are required in order to confirm these data.

Transrectal-HIFU as primary minimally-invasive option for localized prostate cancer. Is spinal anaesthesia cost-effective? A single centre experience in over 100 patients.

INTRODUCTION: The management of Prostate cancer (PC), since PSA testing has been introduced in the clinical practice, has been significantly spoiled by a "leading-time bias" effect. As a consequence, this has brought to a dramatic diagnosis anticipation at the 4th-5th decade of life in sexually active and otherwise asymptomatic men. Standard options as radical prostatectomy or EBRT are hampered by a significant negative impact on patient's QoL. More recently several alternative minimally-invasive ablative treatment modalities have been proposed with promising results. Among these, TR-HIFU (Trans-Rectal High Intensity Focused Ultrasound) is playing a growing role in the treatment of localized low-intermediate risk PC, although long-term oncologic outcome are still awaited. In order to achieve an optimal result, a specific TR-HIFU's requirement is given by an unchanging target throughout the whole procedure. Therefore, the ideal anaesthesia should be either minimally-invasive and allow to get a motionless target up to 3-4 hours. A retrospective evaluation of efficacy and safety of a spinal anaesthesia in this patient's setting was done. MATERIAL AND METHODS: 107 patients with localized prostate cancer treated in our institution from October 2004 to December 2007 with TR-HIFU procedure received a subarachnoidal anaesthesia with combined administration of 0.5% normobaric racemic bupivacaine (15 to 17.5 mg) and sufentanil 5 microg. RESULTS: This technique allowed covering the whole TR-HIFU procedure (analgesia and motor blockade up to 4-5 hours). It was well tolerated by patients who only rarely required additional sedative or analgesics. A low anaesthesia-related side effects rate, as arterial hypotension, nausea and vomiting, and no severe side effects of intrathecal opioids, as deep sedation, bradycardia, myosis, bradypnea and oxygen desaturation, occurred. Intraoperative employment of sedatives and postoperative need of analgesics was low. CONCLUSIONS: Using a low-dose intrathecal sufentanil an effective spinal block either on the sensitive and motor pathways was provided. Patients' tolerance to the procedure was good and the side-effect rate low. No adverse reactions to intrathecal sufentanil 5 microg were observed. In our experience TR-HIFU can be performed with neuraxial block in most of the cases and it's associated to a favorable cost-benefit rate.