What to Do, and What Not to Do, When Diagnosing and Treating Breakthrough Cancer Pain (BTcP): Expert Opinion.

Clinical management of breakthrough cancer pain (BTcP) is still not satisfactory despite the availability of effective pharmacological agents. This is in part linked to the lack of clarity regarding certain essential aspects of BTcP, including terminology, definition, epidemiology and assessment. Other barriers to effective management include a widespread prejudice among doctors and patients concerning the use of opioids, and inadequate assessment of pain severity, resulting in the prescription of ineffective drugs or doses. This review presents an overview of the appropriate and inappropriate actions to take in the diagnosis and treatment of BTcP, as determined by a panel of experts in the field. The ultimate aim is to provide a practical contribution to the unresolved issues in the management of BTcP. Five 'things to do' and five 'things not to do' in the diagnosis and treatment of BTcP are proposed, and evidence supporting said recommendations are described. It is the duty of all healthcare workers involved in managing cancer patients to be mindful of the possibility of BTcP occurrence and not to underestimate its severity. It is vital that all the necessary steps are carried out to establish an accurate and timely diagnosis, principally by establishing effective communication with the patient, the main information source. It is crucial that BTcP is treated with an effective pharmacological regimen and drug(s), dose and administration route prescribed are designed to suit the particular type of pain and importantly the individual needs of the patient.

Percutaneous arthrodesis of sacro-iliac joint: a pilot study.

AIM: Between 15-30% of patients presenting with low back pain have some SI joint involvement. The diagnosis of SI joint involvement in low back pain is quite difficult and depends on a detailed combination of clinical manoeuvres and injection tests. In 5% of patients with SI joint pain, the joint is physically unstable (termed disruption) resulting in ineffective medical and conservative therapeutic options. In this study we present the results of the first 12 cases of SI joint disruption treated using a minimally invasive SI joint arthrodesis system in order to evaluate the safety and the efficacy of this system. METHODS: Medical charts at a single center were reviewed for demographics, perioperative metrics, patient reported outcomes for pain, function and quality of life (NRS, ODI and RDQ respectively), as well as satisfaction with surgery (yes/no) and results of postoperative CT scan. RESULTS: Mean age was 53 years (range 36-71) and all patients were female. Patient reported outcomes at follow up (range 8-18 months) improved clinically as well as statistically as evidenced by a mean improvement in pain on NRS of 4 points, back related function on ODI by 19.4 points, and in quality of life measured using RDQ of 13.6 points (all P=0.01). Local hematoma requiring drainage was apparent in 2 patients. Patient satisfaction was 100%. All 3 month CT scans showed initial fusion. CONCLUSION: The results of this study confirm that MIS SI joint fusion using the iFuse Implant System is safe and effective method of treating patients with SI joint disruption.

Variability in muscle adaptation to electrical stimulation.

The aims were to investigate the plasticity of the myosin heavy chain (MHC) phenotype following neuromuscular electrical stimulation (NMES) and to assess the correlation between MHC isoform distribution and muscle fibre conduction velocity (MFCV).14 men were subjected to 24 sessions of quadriceps NMES. Needle biopsies were taken from the dominant vastus lateralis and neuromuscular tests were performed on the dominant thigh before and after training. NMES significantly increased the quadriceps maximal force by 14.4±19.7% (P=0.02), vastus lateralis thickness by 10.7±8.6% (P=0.01), vastus lateralis MFCV by 11.1±3.5% (P<0.001), vastus medialis MFCV by 8.4±1.8% (P<0.001). The whole spectrum of possible MHC isoform adaptations to training was observed: fast-to-slow transition (4 subjects), bi-directional transformation from MHC-1 and MHC-2X isoforms toward MHC-2A isoform (7 subjects), shift toward MHC-2X (2 subjects), no MHC distribution change (1 subject). No significant correlation was observed between MHC-2 relative content and vastus lateralis MFCV (pre-training: R2=0.04, P=0.46; post-training: R2=0.02, P=0.67). NMES elicited distinct adaptations in the MHC composition and increased force, muscle thickness, and MFCV. The MHC isoform distribution did not correlate with MFCV, thus implying that the proportion of different fibre types cannot be estimated from this electrophysiological variable.

Evaluation of nutritional status and dietary intake in patients with advanced cancer on palliative care.

AIM: Cancer cachexia and malnutrition are very common in patients receiving palliative care. They cause a deterioration in the quality of life. METHODS: We studied 144 patients (52 females, 92 males) admitted to our Palliative Care Unit. Anthropometric measurements, food and nutritional intake, and plasma levels of few serum proteins were determined. Basal metabolic rate (BMR) was calculated. RESULTS: A body mass index (BMI) below 18.5 kg/m2 was observed in 23% of females and in 13% of males (P = NS). Twenty females (44%) and 52 males (63%) showed a weight loss of more than 10% over the 6-month period (P = 0.073). Ten females (19%) and 58 males (63%) had an arm muscle area (AMA) below the 5th percentile (P < 0.001), while 20 females (38%) and 21 males (23%) had an arm fat area (AFA) below the 5th percentile (P = 0.071). The daily calorie intake was below the BMR in 22 females (42%) and in 53 males (58%) (P = NS). Plasma levels of prealbumin, transferrin, and albumin were found below the normal range in more than 70% in both sexes. CONCLUSION: Protein energy malnutrition can be easily detected by anthropometric and laboratory indexes. The larger percentage of males with a reduction in lean body mass compared to females could signify an advantage for females since lean body mass is preserved for longer in them. Patients with advanced cancer receiving palliative care should thus be evaluated routinely to assess their nutritional status in order to plan an adequate nutritional program when appropriate.

[Validazione della versione italiana del Brief Pain Inventory nei pazienti con dolore cronico]. / Validazione della versione italiana del Brief Pain Inventory nei pazienti con dolore cronico.

BACKGROUND: The purpose of this study has been the validation of an Italian version of the Brief Pain Inventory (BPI), Breve Questionario per la valutazione del Dolore (BQVD), in patients with chronic pain not-caused by neoplastic illness. METHODS: The analysis has been proposed to 113 patients affected by different kinds of chronic pain of non-neoplastic origin while hospitalized, both as outpatients or as in-patients. The descriptive analysis of the specimen and of each item of the BPI has been carried out. Moreover, the psychometric characteristics of the analysis, intended as an instrument to describe intensity of pain and its interference in the various aspects of life have been investigated, evaluating with factorial analysis its validity both as a construct, and its internal coherence calculating the Cronbach's alpha of the whole instrument and of each identifier with factorial analysis. RESULTS: From the factorial analysis emerged a frame with three factors that have been identified as Pain intensity, Pain interference in emotional sphere and Interference in working activities. CONCLUSIONS: The Brief Pain Inventory can be considered a suitable useful instrument in the global evaluation of patients affected by chronic pain since its allows a contemporaneous analysis of three factors that characterize the phenomenon and contribute equally in defining the various facet of the pain universe. The Italian version of the BPI may be included in the essential evaluation instruments in the diagnosis and therapy of chronic pain.

[Validation of the Italian version of the "Neuropathic Pain Scale" and its clinical applications]. / Validazione della "Scala del Dolore neuropatico" (SDN) e sue applicazioni terapeutiche.

BACKGROUND: The Neuropathic Pain Scale is the first specific tool to measure and analyse pain due to a lesion in the nervous system; this kind of pain is usually difficult to describe for the patient because it is characterized by unusual qualities. Aim of this study is to evaluate a possible relation between pain descriptions and underlying pathogenetic mechanisms. METHODS: The Italian version of the Neuropathic Pain Scale has been administered to 145 patients with neuropathic pain due to chronic radiculopathy, diabetic neuropathy, post-traumatic neuropathy, Complex Regional Pain Syndrome or postherpetic neuralgia. As it has been done in Galer's study, the predictive validity and the items' correlation have been evaluated; moreover, the structure validity of the scale has been studied. RESULTS: Pain values were high in all pain syndromes with the prevalence of certain items in particular pathologies. The correlation of some items with "deep pain" and others with "superficial pain" was also observed. CONCLUSIONS: The results have confirmed the statistical validity of the Italian version of the scale; they also pointed out the usefulness of the scale to distinguish between superficial pain, typical of neuropathic pain, and deep pain, typical of somatic pain.

[Occupational exposure to vibration: Raynaud's phenomenon and the vascular response to methacholine iontophoresis]. / Esposizione professionale a vibranti: fenomeno di Raynaud e risposta vascolare a ionoforesi con metacolina.

A homogeneous group of 34 subjects exposed to occupational vibratory stress were studied to determine their vasodilatory response to methacoline. The methacoline was administered by iontophoresis. Methacoline is an acetylcholine derivate with the same pharmacological properties of acetylcholine. The 34 study subjects were divided into 3 groups according to their plethysmographic response to a preliminary cold test: group 1, had a typical Raynaud's response; group 2 had normal response to cold, and group 3 had an "intermediate" response. The subjects in group 1 did not respond to methacoline with vasodilation, suggesting endothelial damage at the arterial and arteriolar level, those in group 2 responded with clear vasodilation, and those in group 3 had an intermediate plethysmographic response to methacoline--modest, slowed vasodilation. Based on the results obtained, the authors believe that the true pathogenetic mechanism is an alteration in the vasomotor stability. This change in circulatory homeostasis occur after a vasoconstrictive stimulus, due to vascular endothelium disfunction, in its turn damaged by vibratory microtrauma. This would be the basis for diminished autonomic vascular regulation, mediated by EDRF at the arterial and arteriolar level. It is also probable that the pathogenesis of Raynaud's syndrome in workers exposed to physical or chemical stress has a similar mechanism.

Clinical toxicity of cryopreserved circulating progenitor cells infusion.

BACKGROUND: We evaluated the infusion-related toxicity of cryopreserved autologous circulating progenitor cells transplanted in 22 patients receiving high dose chemotherapy and stem cells transplantation for malignancy. MATERIALS AND METHODS: Progenitor cells were collected following mobilization with chemotherapy plus filgrastim and stored in liquid nitrogen in the presence of 10% dimethylsulfoxide (DMSO). Before infusion of the graft, patients were medicated with mannitol, hydrocortisone and clorphenamine. The amount of DMSO infused as well as the number of dead and damaged cells were evaluated as possible cause of toxicity. RESULTS: Eleven patients (50%) experienced symptoms related to graft infusion, nausea and vomiting being the most common adverse events. Hypotension was documented in 3 patients (one of them developing transient bradycardia resolved with atropin administration) and one had hypertension with tachycardia. Other observed side effects were: chest tightness (2 pts), fever and chills (3 pts), associated with abdominal cramps (2 pts). 7 out of 8 (88%) patients infused with greater than 30 mL volume of DMSO experienced side-effects, the grade of toxicity being significantly less in those receiving lower amount (< 30 mL) of DMSO. Two out of 4 pts who received the highest number of dead cells (> 10 x 10(9)) developed toxicity. CONCLUSIONS: In our experience the infusion of cryopreserved peripheral blood progenitors caused minor to moderate toxicity in most cases and, when present, side effects were observed only during infusion. The amount of DMSO present in the graft is related to the grade of toxicity.

Electromotive administration of a new morphine formulation: morphine citrate.

Two formulations of morphine citrate were synthesized: trimorphine citrate, 3(MH)+(C6H5O7)3- and morphine sodium citrate, 3(MH)+3Na+2(C6H5O7)3-. Four healthy individuals volunteered to undergo electromotive administration of the two formulations. Application of electric current (2 mA) to solutions of trimorphine citrate for 1 h resulted in iontophoretic transcutaneous administration of therapeutic quantities of morphine, without deleterious reduction in the pH of the drug solutions. Application of a 2-mA current to solutions of morphine sodium citrate for 2 h resulted in combined iontophoretic and electrophoretic delivery of morphine with increased administration rates and an improved buffering capacity of the drug solutions.

Electromotive administration of guanethidine for treatment of reflex sympathetic dystrophy: a pilot study in eight patients.

Persistent neuropathic pain is associated with diagnostic and therapeutic challenges that may be very difficult to resolve. This report describes eight patients with incapacitating, posttraumatic neuropathic pain characteristic of reflex sympathetic dystrophy (RSD) who were treated by electromotive administration of guanethidine into affected areas of skin. Following 1-5 treatments, six patients experienced complete resolution of all superficial symptoms of hyperalgesia, pain, pallor, coolness, and sweating of the affected areas. One patient demonstrated partial relief of these symptoms, and one patient failed to respond. The results of this preliminary study suggest that electromotive administration of the the sympatholytic agent, guanethidine, may be useful in the treatment of some types of neuropathic pain. These findings justify the implementation of further controlled studies.