[Non-invasive trans-cranial magnetic resonance imaging-guided focused ultrasounds surgery to treat neurologic disorders]. / Terapia chirurgica trans-cranica non invasiva mediante ultrasuoni focalizzati guidati da risonanza magnetica per il trattamento di disordini neurologici.

In past years non-invasive clinical applications of magnetic resonance-guided focused ultrasound for the treatment of neurological disorders have been hampered by technical limitations that today have been finally overcome. In 2015, for the first time in the world, the very first treatments have been performed in Italy by the use of an affordable 1.5T magnetic resonance unit. The clinical results obtained to date and all the future possible applications are very promising and pave the way towards safe and effective treatment options once unthinkable.

Pharmacological management of cancer pain in children.

The aim of this review was to assess cancer pain management in children on the basis of research published in the last ten years. Nine were papers providing clinical data, with a minimum of ten patients. No controlled studies were found. Regardless of general principles and existing recommendations, clinical data should confirm the applicability of this concept. The trials published in the last years did not provide further information to improve cancer pain management in children, because of the experience and the low number of drugs used, reflecting only meaningful opinions of experts in the field. The amount and the quality of data still remain poor, as only 737 subjects (about 80 patients per year) were surveyed with open-label designs or retrospective analysis. No comparison among possible treatments or drugs has ever been performed. Most of these trials are short-lived and assessment of adverse effects is often problematic. The experience with opioids is quite limited, and adjuvants have been seldom assessed, unless for case reports which have not been considered in this analysis. The management of breakthrough pain has never been specifically evaluated. Further clinical trials are needed to evaluate dose equivalence, clinical efficacy and safety of opioid analgesics, differences in opioid response, adjuvants and other drugs commonly used to manage opioid-related adverse effects, and dose strengths necessary for most children.

Assessment of treatment response in hepatocellular carcinoma: a review of the literature.

Hepatocellular carcinoma (HCC) has a high incidence all over the world. Even if the primary end point of treatment of HCC is survival, radiological response could be a surrogate end point of survival, and could have a key role in clinical management. Since 1950 several radiological response criteria have been applied; however, it was not until 2000 that specific criteria for HCC were introduced by the European Association for the Study of the Liver (EASL), and these were then standardized in 2010 with the development of the modified Response Evaluation Criteria for Solid Tumors (mRECIST) for HCC. The purpose of this brief review is to compare data in literature regarding the application and the performance of mRECIST in clinical practice, and to discuss unclear and open issues.

Treatment of hepatocellular carcinoma: present and future.

Hepatocellular carcinoma is a major health problem. It is the sixth most common cancer worldwide and the third most common cause of cancer-related death. Despite the availability of several treatment opportunities, diagnosis is still made in an advanced phase, limiting application of most therapeutic choices that currently are based on the Barcelona Clinic Cancer Liver Classification and include surgical resection, orthotopic liver transplantation and ablative methods for very early and early disease, arterial chemoembolization for intermediate stages and systemic therapy with sorafenib for advanced hepatocellular carcinoma. Thanks to novel advancements in knowledge of molecular pathogenesis of this tumor, many new systemic agents and locoregional treatments are in different stages of clinical development and they represent an important promise of further improvements in patients' survival.

Opioid switching from and to tapentadol extended release in cancer patients: conversion ratio with other opioids.

OBJECTIVES: The aim of this exploratory study was to assess the conversion ratios between tapentadol and other opioids in patients requiring an opioid switching. METHODS: A prospective study was carried out in a convenience sample of consecutive patients admitted to an acute palliative care unit and a home care unit for a period of 1 year. Patients who were switched from/to tapentadol were selected. The initial ratio between tapentadol and other opioids, expressed as oral morphine equivalents was 1:3.3. The subsequent doses were flexible and were changed to fit the patients' needs. Pain intensity and distress score were recorded until opioid doses were stable. In all, 37 patients were examined; 24 and 13 patients were switched from and to tapentadol, respectively. RESULTS: The most frequent sequences were tapentadol-morphine (18 patients) in one direction, and morphine-tapentadol (8 patients) in the other direction. In the sequence tapentadol-morphine and morphine-tapentadol, the mean final tapentadol-morphine ratios were 3.9:1 (SD 2.3), and 1:4.5 (SD 3.2), respectively, which did not differ significantly from the initial established conversion ratio. A minority of patients were switched from/to tapentadol to/from other opioids. Globally, the initial ratio did not change after switching took place. CONCLUSION: Data suggest that a conversion ratio between tapentadol and other opioids, expressed in oral morphine equivalents could be 1:3.3 in both direction, particularly in patients who are switched in conditions of equianalgesia. The limited number of patients prevents a definitive conclusion to be drawn, and data should be interpreted with caution, given the exploratory nature of the study and the question of the low number of patients should be addressed in future studies.

Opioid use and effectiveness of its prescription at discharge in an acute pain relief and palliative care unit.

The aim of this study was to present how opioids are used in an acute pain relief and palliative care unit (APRPCU), where many patients with difficult pain conditions are admitted from GPs, home palliative care programs, oncology departments, other hospitals or emergency units, and other regional places. From a consecutive sample of cancer patients admitted to an APRPCU for a period of 6 months, patients who had been administered opioids were included in this survey. Basic information was collected as well as opioid therapy prescribed at admission and, subsequently, during admission and at time of discharge. Patients were discharged once stabilization of pain and symptoms were obtained and the treatment was considered to be optimized. One week after being discharged, patients or relatives were contacted by phone to gather information about the availability of opioids at dosages prescribed at time of discharge. One hundred eighty six of 231 patients were specifically admitted for uncontrolled pain, with a mean pain intensity of 6.8 (SD 2.5). The mean dose of oral morphine equivalents in patients receiving opioids before admission was 45 mg/day (range 10-500 mg). One hundred seventy five patients (75.7 %) were prescribed around the clock opioids at admission. About one third of patients changed treatment (opioid or route). Forty two of 175 (24 %), 27/58 (46.5 %), 10/22 (45.4 %), and 2/4 (50 %) patients were receiving more than 200 mg of oral morphine equivalents, as maximum dose of the first, second, third, and fourth opioid prescriptions, respectively. The pattern of opioids changed, with the highest doses administered with subsequent line options. The mean final dose of opioids, expressed as oral morphine equivalents, for all patients was 318 mg/day (SD 798), that is more than six times the doses of pre-admission opioid doses. One hundred eighty six patients (80.5 %) were prescribed a breakthrough cancer pain (BTcP) medication at admission. Sixty five patients changed their BTcP prescription, and further 27 patients changed again. Finally, eight patients were prescribed a fourth BTcP medication. Of 46 patients available for interview, the majority of them (n = 39, 84 %) did not have problems with their GPs, who facilitated prescription and availability of opioids at the dosages prescribed at discharge. For patients with severe distress, APRPCUs may guarantee a high-level support to optimize pain and symptom intensities providing intensive approach and resolving highly distressing situations in a short time by optimizing the use of opioids.

Combined oral prolonged-release oxycodone and naloxone in chronic pain management.

INTRODUCTION: The use of opioids is associated with unwanted adverse effects, particularly opioid-induced constipation (OIC). The adverse effects of opioids on gastrointestinal function are mediated by the interaction with opioid receptors in the gastrointestinal tract. The most common drugs used for relieving OIC are laxatives, which do not address the opioid receptor-mediated bowel dysfunction and do not provide sufficient relief. AREAS COVERED: This paper discusses the role of a combination of prolonged-release formulation of oxycodone (OX) and naloxone (N) in the prevention and management of OIC, reporting efficacy and safety outcome of controlled studies. In a therapeutic area of great unmet need, the combination tablet of prolonged release of OX and N (PR OXN) could offer patients effective analgesia, while improving opioid-induced bowel dysfunction. EXPERT OPINION: PR OXN offers a unique and specific mechanism to control OIC in patients receiving chronic opioid therapy. This combination has the potential advantage of preventing OIC, particularly in subgroups of population, like elderly or advanced cancer patients. This approach can decrease the use of laxatives and additional medications, which represent a burden for patients presenting comorbidities requiring multiple medications.

US Food and Drug Administration's Risk Evaluation and Mitigation Strategy for extended-release and long-acting opioids: pros and cons, and a European perspective.

Prescriptions for opioid analgesics to manage moderate-to-severe chronic non-cancer pain have increased markedly over the last decade. An unintentional consequence of greater prescription opioid utilization has been the parallel increase in misuse, abuse and overdose, which are serious risks associated with all opioid analgesics. In response to disturbing rises in prescription opioid abuse, the US Food and Drug Administration (FDA) has proposed the implementation of aggressive Risk Evaluation and Mitigation Strategies (REMS). While REMS could dramatically change the development, release, marketing and prescription of extended-release opioids, questions remain on how these programmes may influence prescribing practices, patient safety and ultimately patient access to these agents. The extent of the availability and misuse of prescription opioids in Europe is difficult to assess from the data currently available, due in large part to the considerable differences in prescribing patterns and regulations between countries. Balancing the availability of prescription opioids for those patients who have pain, while discouraging illicit use, is a complex challenge and requires effective efforts on many levels, particularly in Europe where policies are quite different between countries.

Tapentadol in cancer pain management: a prospective open-label study.

OBJECTIVES: The aim of this prospective, open-label study was to evaluate the efficacy and tolerability of tapentadol (TP) in the management of cancer pain. METHODS: A 4 weeks' prospective study was carried out in 50 opioid-naive cancer patients with moderate-severe pain. Each patient initially received twice-daily doses of slow-release TP 50 mg. Doses were then managed to maintain adequate relief or dose-limiting toxicity, on the basis of the clinical response. The following parameters were recorded at weekly intervals for 4 weeks: pain and opioid-related adverse effects, quality of life measured with the Spitzer score, TP escalation index percent (TPEI%) and TP escalation index in mg (TPEImg), calculated at the end of the study, pain mechanisms, and PainDETECT at baseline. RESULTS: Of 50 patients, 39 completed the entire study and 11 discontinued the treatment for different reasons. Pain intensity significantly decreased from baseline to all the week intervals (p < 0.0005), and adverse effects did not changed significantly, while quality of life improved. TP escalation indexes were low and no relationship was found with age, gender, and pain mechanisms. CONCLUSION: Tapentalol started in doses of 100 mg/day was well-tolerated and effective in opioid-naive patients with cancer pain, regardless of the pain mechanism. It can be considered as a flexible drug to be used in patients with moderate-severe pain. LIMITATIONS: This was an open-label study for exploratory purposes. Data should be confirmed in controlled studies with a larger number of patients.

The anesthesiologist and end-of-life care.

PURPOSE OF REVIEW: Anesthesiologists may face problematic situations when patients are close to death, in which clinical problems, decision-making processes, and ethical issues are often interconnected and dependent on each of them. The aim of this review is to assess the recent literature regarding the anesthesiological role for advanced cancer patients. RECENT FINDINGS: Palliative sedation in the dying patients, end-of-life problems in the ICU, and pain control in advanced cancer patients have been the subject of recent research. All these issues have shown that anesthesiologist would be expert in the field of pain and symptom control at the end of life. End-of-life care problems are common in ICU, and a decision-making process requires knowledge and management of patients' wishes, past and projected future quality of life, severity and prognosis of illness, patients' age, regarding withholding and withdrawing of futile treatments in anticipation of death, or relieving symptoms close to death. SUMMARY: Anesthesiologists should be competent in all aspects of terminal care, including the practical and ethical aspects of withdrawing different modalities of life-sustaining treatment and the use of sedatives, analgesics, and nonpharmacologic approaches to easing the suffering of the dying process. More research is needed to provide models which should be spread in the scientific community to afford this difficult task.

Effects of red blood cell transfusion on anemia-related symptoms in patients with cancer.

The aim of this study was to assess the effects of red blood cell transfusion, and the subsequent increase in hemoglobin values, on anemia-related symptoms in a cohort of patients with cancer with different survival times. A red blood cell transfusion was recommended to a consecutive sample of patients with hemoglobin levels of 8 +/- 0.5 g/dL. The number of units to be ordered was decided according the hemoglobin values with a mean target of increasing the hemoglobin values by approximately 2 g/dL. Hemoglobin values, anemia-related signs and symptoms, including well-being, fatigue, and dyspnea, were recorded at admission (T0), 1 day after the last transfusion (T1), and 15 days afterward (T2) by telephone contact or visit. Well-being, fatigue, and dyspnea were measured on a numerical scale of 0-10. Sixty-one patients were recruited in the period of study. One hundred thirty-three units of red blood cells were transfused (mean 2.18, 95% confidence interval [CI] 0.6). Complete data were available for 40 patients. Hemoglobin values and well-being significantly increased after transfusion (T1), maintaining acceptable values 15 days afterward (T2). Significant changes in fatigue and dyspnea were found immediately after transfusion, although the effect was partially lost 15 days after transfusion. No statistical differences were found between patients with different survival times. Fatigue was significantly lower in patients with longer survival times in comparison with patients with shorter survival times (p = 0.04). Blood transfusion in patients with hemoglobin values of approximately 8 g/dL improved anemia-related symptoms on a short-term basis. This benefit is independent of the stage of disease and survival. However, the effects on dyspnea and fatigue tend to decrease within 15 days, despite the maintenance of hemoglobin values attained after transfusions, suggesting that other factors may play a role.

Equipotent doses to switch from high doses of opioids to transdermal buprenorphine.

INTRODUCTION: The aim of this study was to evaluate the equianalgesic ratio of transdermal buprenorphine (TD BUP) with oral morphine and TD fentanyl in a sample of consecutive cancer patients receiving stable doses of 120-240 mg of oral morphine or 50-100 microg of TD fentanyl, reporting adequate pain and symptom control. MATERIALS, METHODS, AND RESULTS: Patients receiving daily stable doses of opioids for more than 6 days, with no more than two doses of oral morphine (20 and 40 mg, respectively) as needed, were switched to TD BUP using a fentanyl-BUP ratio of 0.6:0.8 and an oral morphine-BUP ratio of 70:1. Opioid doses, pain and symptom intensity, global satisfaction, and number of breakthrough medication were recorded before switching (T0), 3 days after (T3), and 6 days after (T6). Eleven patients were recruited in a period of 1 year, and data were complete for ten patients. The mean age was 61.6 (SD 9.5), and five patients were males. No significant changes in pain and symptom intensity were found, except improvement in reported constipation (p = 0.014), as well as in global satisfaction with the analgesic treatment. No significant changes in breakthrough pain medication were observed. CONCLUSION: The results of this study suggest that stable patients receiving relatively high doses of oral morphine or TD fentanyl could be safely switched to TD BUP, by using a ratio of 70:1 and 0.6:0.8, respectively, maintaining the same level of analgesia.