Does sodium oxybate inhibit brain dopamine release in humans? An exploratory neuroimaging study.

OBJECTIVE: To establish in an exploratory neuroimaging study whether γ-hydroxybutyrate (sodium oxybate [SO]), a sedative, anti-narcoleptic drug with abuse potential, transiently inhibits striatal dopamine release in the human. METHODS: Ten healthy participants (30 years; 6M, 4F) and one participant with narcolepsy received a baseline positron emission tomography scan of [C-11]raclopride, a D2/3 dopamine receptor radioligand sensitive to dopamine occupancy, followed approximately one week later by an oral sedative 3g dose of SO and two [C-11]raclopride scans (1 h, 7 h post SO). Plasma SO levels and drowsiness duration were assessed. RESULTS: No significant changes were detected in [C-11]raclopride binding in striatum overall 1 or 7 h after SO, but a small non-significant increase in [C-11]raclopride binding, implying decreased dopamine occupancy, was noted in limbic striatal subdivision at one hour (+6.5%; p uncorrected = 0.045; +13.2%, narcolepsy participant), returning to baseline at 7 h. A positive correlation was observed between drowsiness duration and percent change in [C-11]raclopride binding in limbic striatum (r = 0.73; p = 0.017). CONCLUSIONS: We did not find evidence in this sample of human subjects of a robust striatal dopamine change, as was reported in non-human primates. Our preliminary data, requiring extension, suggest that a 3g sedative SO dose might cause slight transient inhibition of dopamine release in limbic striatum.

MR-guided prostate biopsy for planning of focal salvage after radiation therapy.

PURPOSE: To determine if the integration of diagnostic magnetic resonance (MR) imaging and MR-guided biopsy would improve target delineation for focal salvage therapy in men with prostate cancer. MATERIALS AND METHODS: Between September 2008 and March 2011, 30 men with biochemical failure after radiation therapy for prostate cancer provided written informed consent and were enrolled in a prospective clinical trial approved by the institutional research ethics board. An integrated diagnostic MR imaging and interventional biopsy procedure was performed with a 1.5-T MR imager by using a prototype table and stereotactic transperineal template. Multiparametric MR imaging (T2-weighted, dynamic contrast material-enhanced, and diffusion-weighted sequences) was followed by targeted biopsy of suspicious regions and systematic sextant sampling. Biopsy needle locations were imaged and registered to diagnostic images. Two observers blinded to clinical data and the results of prior imaging studies delineated tumor boundaries. Area under the receiver operating characteristic curve (Az) was calculated based on generalized linear models by using biopsy as the reference standard to distinguish benign from malignant lesions. RESULTS: Twenty-eight patients were analyzed. Most patients (n = 22) had local recurrence, with 82% (18 of 22) having unifocal disease. When multiparametric volumes from two observers were combined, it increased the apparent overall tumor volume by 30%; however, volumes remained small (mean, 2.9 mL; range, 0.5-8.3 mL). Tumor target boundaries differed between T2-weighted, dynamic contrast-enhanced, and diffusion-weighted sequences (mean Dice coefficient, 0.13-0.35). Diagnostic accuracy in the identification of tumors improved with a multiparametric approach versus a strictly T2-weighted or dynamic contrast-enhanced approach through an improvement in sensitivity (observer 1, 0.65 vs 0.35 and 0.44, respectively; observer 2, 0.82 vs 0.64 and 0.53, respectively; P < .05) and improved further with a 5-mm expansion margin (Az = 0.85 vs 0.91 for observer 2). After excluding three patients with fewer than six informative biopsy cores and six patients with inadequately stained margins, MR-guided biopsy enabled more accurate delineation of the tumor target volume be means of exclusion of false-positive results in 26% (five of 19 patients), false-negative results in 11% (two of 19 patients) and by guiding extension of tumor boundaries in 16% (three of 19 patients). CONCLUSION: The integration of guided biopsy with diagnostic MR imaging is feasible and alters delineation of the tumor target boundary in a substantial proportion of patients considering focal salvage.

Incidence of urinary retention in patients with thoracic patient-controlled epidural analgesia (TPCEA) undergoing thoracotomy.

Up to 100% of patients treated with epidural analgesia can experience urinary retention, which may be related to dermatomal level of the epidural block, epidural medication, and surgical procedure. This study was designed to identify the incidence of urinary retention in patients who receive thoracic patient-controlled epidural analgesia (TPCEA) after thoracotomy. Forty-nine patients were enrolled and received epidural infusion of ropivacaine 0.2% or mixture of bupivacaine 0.1% with hydromorphone 0.015 mg/mL. Epidural catheter placement level was verified by chest X-rays. Indwelling urinary catheters were removed between 12 and 48 h after surgery when no longer required for fluid monitoring. Four hours later, patients were assessed for urinary retention using bladder ultrasound. Residual bladder volume was recorded, and urinary retention was defined as an inability to void or a bladder volume of greater than 600 mL at 4 h. Twenty-four hours after the catheter removal, patients completed a questionnaire to assess their perception of the indwelling catheter before and after its removal. Five participants (approximately 10%) with epidural catheters between T3 and T5 with bupivacaine/hydromorphone epidural solution were recatheterized. No association was established between catheter level, drug type, infusion rate, and urinary retention. Although 76% of patients did not report any physical discomfort with the indwelling urinary catheter, 66% felt relief after its removal and 18% did not ambulate with the inserted urinary catheter. The incidence of postoperative urine retention was low (10%), indicating that unless required for other purposes, indwelling urinary catheters may be removed between 12 and 48 h after surgery while receiving TPCEA.

Dosimetric impact of intrafraction changes in MR-guided high-dose-rate (HDR) brachytherapy for prostate cancer.

PURPOSE: To assess changes in implant and treatment volumes through the course of a prostate high-dose-rate brachytherapy procedure and their impact on plan quality metrics. METHODS AND MATERIALS: Sixteen MRI-guided high-dose-rate procedures included a post-treatment MR (ptMR) immediately after treatment delivery (135 min between MR scans). Target and organs at risk (OARs) were contoured, and catheters were reconstructed. The delivered treatment plan was applied to the ptMR image set. Volumes and dosimetric parameters in the ptMR were evaluated and compared with the delivered plan using a paired two-tailed t-test with p < 0.05 considered statistically significant. RESULTS: An average increase of 8.9% in prostate volume was observed for whole-gland treatments, resulting in reduction in coverage for both prostate and planning target volume, reflected in decreased V100 (mean 3.3% and 4.6%, respectively, p < 0.05), and D90 (mean 7.1% and 7.6%, respectively, of prescription dose, p < 0.05). There was no significant change in doses to OARs. For partial-gland treatments, there was an increase in planning target volume (9.1%), resulting in reduced coverage and D90 (mean 3.6% and 12.4%, respectively, p < 0.05). A decrease in D0.5cc for bladder (3%, p < 0.05) was observed, with no significant changes in dose to other OARs. CONCLUSIONS: Volumetric changes were observed during the time between planning MR and ptMR. Nonetheless, treatment plans for both whole- and partial-gland therapies remained clinically acceptable. These results apply to clinical settings in which patients remain in the same position and under anesthesia during the entire treatment process.

Evaluation of a low-cost, 3D-printed model for bronchoscopy training.

BACKGROUND: Flexible bronchoscopy is a fundamental procedure in anaesthesia and critical care medicine. Although learning this procedure is a complex task, the use of simulation-based training provides significant advantages, such as enhanced patient safety. Access to bronchoscopy simulators may be limited in low-resource settings. We have developed a low-cost 3D-printed bronchoscopy training model. METHODS: A parametric airway model was obtained from an online medical model repository and fabricated using a low-cost 3D printer. The participating physicians had no prior bronchoscopy experience. Participants received a 30-minute lecture on flexible bronchoscopy and were administered a 15-item pre-test questionnaire on bronchoscopy. Afterwards, participants were instructed to perform a series of predetermined bronchoscopy tasks on the 3D printed simulator on 4 consecutive occasions. The time needed to perform the tasks and the quality of task performance (identification of bronchial anatomy, technique, dexterity, lack of trauma) were recorded. Upon completion of the simulator tests, participants were administered the 15-item questionnaire (post-test) once again. Participant satisfaction data on the perceived usefulness and accuracy of the 3D model were collected. A statistical analysis was performed using the t-test. Data are reported as mean values (± standard deviation). RESULTS: The time needed to complete all tasks was 152.9 ± 71.5 sec on the 1st attempt vs. 98.7 ± 40.3 sec on the 4th attempt (P = 0.03). Likewise, the quality of performance score improved from 8.3 ± 6.7 to 18.2 ± 2.5 (P < 0.0001). The average number of correct answers in the questionnaire was 6.8 ± 1.9 pre-test and 13.3 ± 3.1 post-test (P < 0.0001). Participants reported a high level of satisfaction with the perceived usefulness and accuracy of the model. CONCLUSIONS: We developed a 3D-printed model for bronchoscopy training. This model improved trainee performance and may represent a valid, low-cost bronchoscopy training tool.

Lessons learned using an MRI-only workflow during high-dose-rate brachytherapy for prostate cancer.

PURPOSE: We report clinical observations of a technique using an MRI-only workflow for catheter insertion and treatment planning in patients receiving standard-care high-dose-rate brachytherapy before external beam radiotherapy for prostate cancer. METHODS AND MATERIALS: Forty patients with intermediate or high-risk prostate cancer were enrolled on a prospective clinical trial approved by our institution's research ethics board. Multiparametric MRI with stereotactic navigation was used to guide insertion of brachytherapy catheters, followed by MRI-based treatment planning. RESULTS: Sixty-two implants were performed. Median catheter insertion + imaging time was 100 minutes, and overall anesthesia time was 4.0 hours (range, 2.1-6.9 hours). MRI at the time of brachytherapy restaged 14 patients (35%) who were found to have a higher stage of disease. In 6 patients, this translated in directed insertion of brachytherapy catheters outside the prostate boundary (extracapsular disease [n = 2] or seminal vesicle invasion [n = 4]). Most patients (80%) had gross tumor visible on MRI, which influenced catheter insertion and treatment planning. MRI depicted postimplant anatomic boundaries clearly, with the exception of the apical prostate which was blurred by trauma after catheter insertion. Conventional dose-planning objectives for the rectum (V75 < 1.0 cc) were difficult to achieve, but toxicities were low (acute grade ≥ 2 genitourinary = 20%, late grade ≥ 2 genitourinary = 15%, and late grade ≥ 2 gastrointestinal = 7%). Urethral trauma visualized on MRI led to two transient Grade 3 events. CONCLUSIONS: Despite a standard-care approach, MRI acquired throughout the procedure altered catheter insertion and dose-planning strategies. An MRI-only workflow is feasible but must be streamlined for broader acceptance.

The Toronto General Hospital Transitional Pain Service: development and implementation of a multidisciplinary program to prevent chronic postsurgical pain.

Chronic postsurgical pain (CPSP), an often unanticipated result of necessary and even life-saving procedures, develops in 5-10% of patients one-year after major surgery. Substantial advances have been made in identifying patients at elevated risk of developing CPSP based on perioperative pain, opioid use, and negative affect, including depression, anxiety, pain catastrophizing, and posttraumatic stress disorder-like symptoms. The Transitional Pain Service (TPS) at Toronto General Hospital (TGH) is the first to comprehensively address the problem of CPSP at three stages: 1) preoperatively, 2) postoperatively in hospital, and 3) postoperatively in an outpatient setting for up to 6 months after surgery. Patients at high risk for CPSP are identified early and offered coordinated and comprehensive care by the multidisciplinary team consisting of pain physicians, advanced practice nurses, psychologists, and physiotherapists. Access to expert intervention through the Transitional Pain Service bypasses typically long wait times for surgical patients to be referred and seen in chronic pain clinics. This affords the opportunity to impact patients' pain trajectories, preventing the transition from acute to chronic pain, and reducing suffering, disability, and health care costs. In this report, we describe the workings of the Transitional Pain Service at Toronto General Hospital, including the clinical algorithm used to identify patients, and clinical services offered to patients as they transition through the stages of surgical recovery. We describe the role of the psychological treatment, which draws on innovations in Acceptance and Commitment Therapy that allow for brief and effective behavioral interventions to be applied transdiagnostically and preventatively. Finally, we describe our vision for future growth.