ABSTRACT
BACKGROUND: Pancreatic cancer is a malignant neoplasm with a high mortality rate, often associated with a delayed diagnosis, the early occurrence of metastasis and an overall, poor response to chemotherapy and radiotherapy. Pain management in pancreatic cancer consists mainly of pharmacological treatment according to the WHO analgesic ladder. Surgical treatment for pain relief, such as splanchnicectomy, is considered amongst the final step of pain management. It has been proven that splanchnicectomy is a safe procedure with a small percentage of complications, nevertheless, it is often used as a last resort, which can significantly decrease its effectiveness. Performance of thoracoscopic splanchnicectomy along the first step of the analgesic ladder may lead to long-lasting protection against the presence and severity of pain. METHODS/DESIGN: A prospective, open label, 1:1 randomized, controlled trial, conducted at a single institution to determine the effectiveness of invasive treatment of pain via splanchnicectomy, in patients with advanced pancreatic cancer. The size of tested group will consist of 26 participants in each arm of the trial, to evaluate the level of pain relief and its impact on quality of life. To evaluate the influence on patients' rate of overall survival, a sample size of 105 patients is necessary, in each trial arm. Assessments will not only include the usage of analgesic pharmacotherapy throughout the course of disease, and overall patient survival, but also subjective pain perception at rest, in movement, and after meals (measured by NRS score questionnaire), the patient's quality of life (measured using the QLQ-C30 and FACIT questionnaires), and any pain-related suffering (measured with the PRISM projection test). The primary endpoint will consist of pain intensity. Questionnaires will be obtained upon the initial visit, the day of surgery, the day after surgery, as well as during long-term follow-up visits, held every two weeks thereafter. DISCUSSION: Earlier implementation of invasive treatment, such as thoracoscopic splanchnicectomy, can provide a higher efficacy of pain management, prevent deterioration in the patient's quality of life, and lengthen their overall survival. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT02424279. Date of registration January 2, 2015.
Subject(s)
Analgesics/therapeutic use , Pain, Intractable/etiology , Pain, Intractable/therapy , Pancreatic Neoplasms/complications , Splanchnic Nerves/surgery , Adult , Female , Humans , Male , Middle Aged , Pain Measurement , Pancreatic Neoplasms/diagnosis , Pancreatic Neoplasms/therapy , Prospective Studies , Quality of Life , Surveys and Questionnaires , Treatment Outcome , World Health OrganizationABSTRACT
Ultrathin "one-component" multilayer polymeric films for potential biomedical applications were designed based on polyvinyl alcohol,-a non-toxic, fully degradable synthetic polymer. Good uniformity of the obtained film and adequate adsorption properties of the polymeric layers were achieved by functional modification of the polymer, which involved synthesis of cationic and anionic derivatives. Synthesized polymers were characterized by FTIR, NMR spectroscopy, dynamic light scattering measurements and elemental analysis. The layer by layer assembly technique was used to build up a multilayer film and this process was followed using UV-Vis spectroscopy and ellipsometry. The morphology and thickness of the obtained multilayered film material was evaluated by atomic force microscopy (AFM). Preliminary studies on the application of the obtained multilayer film for coating of liposomal nanocarriers containing phenytoin, an antiarrhythmic drug, were performed. The coating effectively stabilizes liposomes and the effect increases with an increasing number of deposited layers until the polymeric film reaches the optimal thickness. The obtained release profiles suggest that bilayer-coated liposomes release phenytoin less rapidly than uncoated ones. The cytotoxicity studies performed for all obtained nanocarriers confirmed that none of them has negative effect on cell viability. All of the performed experiments suggest that liposomes coated with ultrathin film obtained from PVA derivatives can be attractive drug nanocarriers.
Subject(s)
Anti-Arrhythmia Agents/administration & dosage , Phenytoin/administration & dosage , Polyvinyl Alcohol/chemistry , Adult , Anti-Arrhythmia Agents/chemistry , Anti-Arrhythmia Agents/toxicity , Cell Survival/drug effects , Delayed-Action Preparations , Drug Carriers , Drug Delivery Systems , Fibroblasts/drug effects , Fibroblasts/metabolism , Humans , Liposomes , Microscopy, Atomic Force , Phenytoin/chemistry , Phenytoin/toxicity , SolubilityABSTRACT
The properties of heparin, a key anticoagulant, are reviewed. The important issues in heparinotherapy, i.e., reaching quick anticoagulant effect, maintaining therapeutic level of anticoagulation, heparin inhibition and non-invasive heparin formulations have been reviewed and discussed, with the focus on the role of polymeric substances in the proposed solutions.