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The effective assessment of cancer pain requires a meticulous analysis of all the components that shape the painful experience collectively. Implementing Automatic Pain Assessment (APA) methods and computational analytical approaches, with a specific focus on emotional content, can facilitate a thorough characterization of pain. The proposed approach moves towards the use of automatic emotion recognition from speech recordings alongside a model we previously developed to examine facial expressions of pain. For training and validation, we adopted the EMOVO dataset, which simulates six emotional states (the Big Six). A Neural Network, consisting of a Multi-Layered Perceptron, was trained on 181 prosodic features to classify emotions. For testing, we used a dataset of interviews collected from cancer patients and selected two case studies. Speech annotation and continuous facial expression analysis (resulting in pain/no pain classifications) were carried out using Eudico Linguistic Annotator (ELAN) version 6.7. The model for emotion analysis achieved 84% accuracy, with encouraging precision, recall, and F1-score metrics across all classes. The preliminary results suggest the potential use of artificial intelligence (AI) strategies for continuous estimation of emotional states from video recordings, unveiling predominant emotional states, and providing the ability to corroborate the corresponding pain assessment. Despite limitations, the proposed AI framework exhibits potential for holistic and realtime pain assessment, paving the way for personalized pain management strategies in oncological settings. Clinical Trial registration: NCT04726228. [ABSTRACT FROM AUTHOR]

COVID-19 pandemic following the outbreak in China and Western Europe, where it finally lost the momentum, is now devastating North and South America. It has not been identified the reason and the molecular mechanisms of the two different patterns of the pulmonary host responses to the virus from a minimal disease in young subjects to a severe distress syndrome (ARDS) in older subjects, particularly those with previous chronic diseases (including diabetes) and cancer. The Management of the Istituto Nazionale Tumori - IRCCS "Fondazione Pascale" in Naples (INT-Pascale), along with all Health professionals decided not to interrupt the treatment of those hospitalized and to continue, even if after a careful triage in order not to allow SARS-CoV-2 positive subjects to access, to take care of cancer patients with serious conditions. Although very few (n = 3) patients developed a symptomatic COVID-19 and required the transfer to a COVID-19 area of the Institute, no patients died during the hospitalization and completed their oncology treatment. Besides monitoring of the patients, all employees of the Institute (physicians, nurses, researchers, lawyers, accountants, gatekeepers, guardians, janitors) have been tested for a possible exposure. Personnel identified as positive, has been promptly subjected to home quarantine and subdued to health surveillance. One severe case of respiratory distress has been reported in a positive employees and one death of a family member. Further steps to home monitoring of COVID-19 clinical course have been taken with the development of remote Wi-Fi connected digital devices for the detection of early signs of respiratory distress, including heart rate and oxygen saturation. In conclusion cancer care has been performed and continued safely also during COVID-19 pandemic and further remote home strategies are in progress to ensure the appropriate monitoring of cancer patients. [ABSTRACT FROM AUTHOR]

Background: The aim of this study was to identify potential variables influencing the clinical presentation of breakthrough cancer pain (BTP). Methods: Cancer patients with a diagnosis of BTP were enrolled. Demographic and clinical characteristics, as well as background pain and BTP characteristics were collected. Multivariate analyses were conducted to assess the correlation between BTP characteristics and the variables examined. Results: Data of 4016 patients were analysed. Average daily number of BTP episodes was 2.4, mean intensity was 7.5, and a mean duration was 43.3 min. A short onset BTP was observed in 68.9% of patients. In 30.5% of patients BTP was predictable. There were 86.0% of participants who reported a marked interference of BTP with their daily activities. Furthermore, 86.8% of patients were receiving opioids for the management of BTP. The average time to meaningful pain relief was 16.5 min and 70.9% of patients were satisfied with their BTP medications. Age, head and neck cancer, Karnofsky, background pain intensity, predictable and fast onset BTP were independently associated with the number of BTP episodes. BTP pain intensity was independently associated with background pain intensity, fast onset BTP, and Karnofsky. Neuropathic pain mechanism was independently associated with unpredictable BTP. Variables independently associated with a longer duration of BTP were age, place of visit, cancer diagnosis, disease-oriented therapy, background pain intensity and mechanism, and unpredictable BTP. Age, Karnofsky, background pain intensity, fast onset, and long duration of BTP were independently associated with interference with daily activity. Conclusions: BTP has a variable presentation depending on interdependent relationships among its different characteristics. [ABSTRACT FROM AUTHOR]

Cannabis as a therapeutic agent is increasing in popularity all around the globe, particularly in Western countries, and its potential is now well assessed. On the other hand, each country has its own regulation for the preparation of cannabis macerated oils; in Italy, there are only a few preparation methods allowed. With this work, we aim to perform a stability study of cannabis oils produced with a novel method for the extraction of cannabinoids from cannabis inflorescence. Three different varieties of cannabis were used, with and without the adding of tocopherol acetate as an antioxidant. Cannabinoids were extracted using ethanol at room temperature; then, the solvent was evaporated under reduced pressure and the preparations reconstituted with olive oil. In this work, we assessed the stability of both cannabinoids and terpenes in these formulas over 8 months. Cannabinoid stability was assessed by monitoring the concentrations of THC and CBD, while terpene stability was assessed by monitoring β -Caryophyllene and α -Humulene concentrations. Stability of the extracts was not influenced by the presence of tocopherol acetate, though refrigeration seems to be detrimental for a long storage of products, especially regarding THC concentrations. The improvements offered by this method reside in the flexibility in controlling the concentration of the extract and the ability to produce highly concentrated oils, alongside the possibility to produce standardized oils despite the variability of the starting plant material., Competing Interests: The authors declare that they have no conflict of interest., (Thieme. All rights reserved.)

Cancer pain is an important challenge in treatment and requires a rapid onset of action for its control. In particular, breakthrough cancer pain (BTcP) should be adequately controlled with a stable dose of a short-acting oral opioid. Fentanyl is a synthetic, highly selective opioid with many advantageous chemical properties, including high lipophilicity and distinct pharmacokinetic properties. It is recommended for pain management in a variety of settings, including acute pain, chronic pain and BTcP. To date, its variously designed formulations allow non-invasive administration; amongst others, sublingual fentanyl has proven useful in the management of BTcP and in improving the quality of life of patients with cancer. This review provides an update on the management of BTcP with fentanyl, with consideration of safety, as it remains an important tool in the treatment of cancer pain., Competing Interests: Disclosure and potential conflicts of interest: The author declares that he has no conflicts of interest relevant to this manuscript. The International Committee of Medical Journal Editors (ICMJE) Potential Conflicts of Interests form for the authors is available for download at: https://www.drugsincontext.com/wp-content/uploads/2023/11/dic.2023-10-2-COI.pdf, (Copyright © 2023 Cuomo A.)

Although proper pain evaluation is mandatory for establishing the appropriate therapy, self-reported pain level assessment has several limitations. Data-driven artificial intelligence (AI) methods can be employed for research on automatic pain assessment (APA). The goal is the development of objective, standardized, and generalizable instruments useful for pain assessment in different clinical contexts. The purpose of this article is to discuss the state of the art of research and perspectives on APA applications in both research and clinical scenarios. Principles of AI functioning will be addressed. For narrative purposes, AI-based methods are grouped into behavioral-based approaches and neurophysiology-based pain detection methods. Since pain is generally accompanied by spontaneous facial behaviors, several approaches for APA are based on image classification and feature extraction. Language features through natural language strategies, body postures, and respiratory-derived elements are other investigated behavioral-based approaches. Neurophysiology-based pain detection is obtained through electroencephalography, electromyography, electrodermal activity, and other biosignals. Recent approaches involve multimode strategies by combining behaviors with neurophysiological findings. Concerning methods, early studies were conducted by machine learning algorithms such as support vector machine, decision tree, and random forest classifiers. More recently, artificial neural networks such as convolutional and recurrent neural network algorithms are implemented, even in combination. Collaboration programs involving clinicians and computer scientists must be aimed at structuring and processing robust datasets that can be used in various settings, from acute to different chronic pain conditions. Finally, it is crucial to apply the concepts of explainability and ethics when examining AI applications for pain research and management., Competing Interests: The authors declare that there are no conflicts of interest., (Copyright © 2023 Marco Cascella et al.)

Background: The utilization of artificial intelligence (AI) in healthcare has significant potential to revolutionize the delivery of medical services, particularly in the field of telemedicine. In this article, we investigate the capabilities of a specific deep learning model, a generative adversarial network (GAN), and explore its potential for enhancing the telemedicine approach to cancer pain management., Materials and Methods: We implemented a structured dataset comprising demographic and clinical variables from 226 patients and 489 telemedicine visits for cancer pain management. The deep learning model, specifically a conditional GAN, was employed to generate synthetic samples that closely resemble real individuals in terms of their characteristics. Subsequently, four machine learning (ML) algorithms were used to assess the variables associated with a higher number of remote visits., Results: The generated dataset exhibits a distribution comparable to the reference dataset for all considered variables, including age, number of visits, tumor type, performance status, characteristics of metastasis, opioid dosage, and type of pain. Among the algorithms tested, random forest demonstrated the highest performance in predicting a higher number of remote visits, achieving an accuracy of 0.8 on the test data. The simulations based on ML indicated that individuals who are younger than 45 years old, and those experiencing breakthrough cancer pain, may require an increased number of telemedicine-based clinical evaluations., Conclusion: As the advancement of healthcare processes relies on scientific evidence, AI techniques such as GANs can play a vital role in bridging knowledge gaps and accelerating the integration of telemedicine into clinical practice. Nonetheless, it is crucial to carefully address the limitations of these approaches., (© 2023. The Author(s).)

Prompt and appropriate treatment of chronic low back pain (cLBP) is of the utmost importance for preventing relevant disability, high burden of disease, and increasing costs for the healthcare system. Recently, the concept of functional impairment has been associated with any type of chronic pain, and mounting attention has been paid to extending the aims of treatment beyond mere pain remission, including restoration of working capacity, everyday functioning, mobility, and quality of life. Nevertheless, a shared definition of functionality is still lacking. Notably, different specialists involved in the treatment of cLBP such as general practitioners, orthopedists, pain therapists, and physiatrists, and patients themselves have different opinions on what "functional impairment" actually means. On these premises, a qualitative interview study was performed to investigate how the concept of "functionality" is interpreted by different specialists involved in the management of cLBP, and by patients. Overall, all different specialists agreed that functionality should be assessed in clinical practice. However, in spite of several instruments available for evaluating functionality, no homogeneity of behavior is observable.

Purpose: Fulfilling educational needs in pain management should be a lifelong process, even involving physicians board certified in pain medicine such as the anesthesiologists/pain therapists. The aim of the study was to investigate Italian anesthesiologists' self-perceived competency, confidence, and interest to attend educational programs in relation to their seniority in pain management., Methods: SIAARTI members were sent an online questionnaire addressing the following items: education, skills (both soft and hard skills), technical expertise and engaged to participate between December 2020 and January 2021. Participants rated their competence based on the following range (no knowledge, knowledge, competence) while their agreement to attend educational courses was assessed using a 5-point Likert-type scale., Results: Less than one in four participants declare to be dedicated to pain medicine activity with greater proportion among older (over 61 years) compared to younger ones (31-40 years). Regarding cancer and chronic noncancer pain a positive gradient of self-perceived competence has been observed in relation to seniority. In contrast, no gradient of self-perceived competence was reported about musculoskeletal and low back pain. Participants self-perceived competent in both opioid use and prevention of opioid-related adverse event while feeling less competent when managing drugs with abuse potential. The lowest competence has been observed in pediatric pain along with the lowest interest to attend educational courses. Participants were much and very much interested to education regarding cancer, noncancer, musculoskeletal, and low back pain, invasive analgesic procedures but less regarding items for which they declared less competence, such as use of pain scales, pain management in children, and use of drugs with abuse potential., Conclusion: This work provides first evidence of a summative assessment of competency and related educational needs' profile of anesthesiologists/pain therapists thus paving the way for developing a nationwide educational program to improve chronic pain care in Italy., (© 2023 The Authors. Pain Practice published by Wiley Periodicals LLC on behalf of World Institute of Pain.)

Cancer pain requires careful comprehensive patient evaluation and an appropriate and personalized clinical approach by a trained multidisciplinary team. The proper assessment of breakthrough cancer pain (BTcP) is part of an all-inclusive multidimensional evaluation of the patient. The aim of this narrative review is to explore the relationship between high-rate BTcP, which strongly impacts health- related quality of life and tumour characteristics, in the face of novel approaches that should provide guidance for future clinical practice. The presentation of short, emblematic clinical reports also promotes knowledge of BTcP, which, despite the availability of numerous therapeutic approaches, remains underdiagnosed and undertreated. This article is part of the Management of breakthrough cancer pain Special Issue: https://www.drugsincontext.com/special_issues/management-of-breakthrough-cancer-pain., Competing Interests: Disclosure and potential conflicts of interest: AB and FC received honoraria from Angelini Pharma S.p.A. AC and DN declare no conflicts of interest. The International Committee of Medical Journal Editors (ICMJE) Potential Conflicts of Interests form for the authors is available for download at: https://www.drugsincontext.com/wp-content/uploads/2023/02/dic.2022-11-1-COI.pdf, (Copyright © 2023 Cuomo A, Boutis A, Colonese F, Nocerino D.)

Triple negative breast cancer (TNBC) represents an aggressive subtype of breast cancer, which is deficient in estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) expression. Thus, TNBC cells are unable to respond to the conventional hormonal therapies, making chemotherapy the only therapeutic choice. Patients with TNBC develop metastasis and recurrence over time and have reduced survival compared to patients with other subtypes of breast cancer. Therefore, there is a need for innovative therapies. Data emerged from pre-clinical studies, highlighted various antitumor activities of plant-derived Cannabis sativa and synthetic cannabinoids (CBs), including delta-9-tetrahydrocannabinol (THC) and non-psychoactive cannabidiol (CBD). On the contrary, some studies indicated that CBs might also promote tumor progression. At present, clinical studies on the effects of CBs from Cannabis sativa in cancer patients are few. In the present study, we reviewed known and possible interactions between cannabinoids and TNBC therapies., (Copyright © 2023 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background/aim: Telemedicine, the remote delivery of healthcare services, represents a great opportunity for cancer pain management. A care model of telemedicine that combines remote visits and hospital access could be an effective and safe strategy for pain management of cancer patients., Patients and Methods: A retrospective study was conducted using the dataset of the telemedicine program at the Istituto Nazionale Tumori of Naples, Italy for assessing the efficacy of a telehealth-based model of care. Demographic, clinical, and process variables were investigated., Results: A total of 226 cases and 489 visits were included in the analysis. The mean age of patients was 63.4 years (SD=12.4 years), and no sex differences were observed. Approximately 55% of patients were ECOG-PS ≤2 and 87% suffered from metastatic disease. More than half of the patients were treated with high doses of opioids. Each patient had a mean of 2 remote visits and half of the patients had more than 1 telehealth consultation. The dropout ratio was 5.3%. Most visits (n=472) were conducted on patients in the Campania Region, Italy. The maximum covered distance from the Cancer Center and the patients' location was 555.22 Km. A significant difference in the overall number of visits (p=0.006) and the number of pro-capita remote visits (p=0.010) was found, in favor of the group of patients treated before the end of the Covid-19 emergency in Italy, compared to those treated after the pandemic., Conclusion: Despite various positive outcomes, the analysis highlights several weaknesses, such as the need to assist patients with advanced and non-advanced disease located outside the regional territory. Overall, the telehealth processes should be adapted to post-pandemic scenarios towards their implementation in routine clinical practice., (Copyright © 2023, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Appropriate pain care should be regarded as a right and effectively guaranteed to people with chronic pain (CP). Law 38, enacted in Italy in 2010, establishes the citizen's right not to suffer. Twelve years later, such right appears still disregarded in Italy and the current access to adequate pain care reveals significant shortcomings. In addition, a mismatch between CP-associated burden and the available healthcare resources in the framework of our national health system has been observed. This article gathers the perspectives of a Board of Italian anesthesiologists on the state of the art of CP management in Italy and aims at strengthening the scientific rationale and clinical relevance of pursuing the enforceability of the right not to suffer and at promoting widespread multidisciplinary care of patients with CP.

Chemotherapy-induced peripheral neuropathy (CIPN) develops as a challenging nerve-damaging adverse effect of anticancer drugs used in chemotherapy. The disorder may require a chemotherapy dose reduction and a cessation of administration of chemotherapeutic drugs. Its principal sensory symptoms include, tingling, and numbness in the hands and feet. Severe pain can be encompassed among clinical manifestations. CIPN affects dramatically the patient's quality of life (QoL). Pain and sensory symptoms may occur for months, or even years after the termination of chemotherapeutic drugs. Although many pharmacological and non-pharmacological therapeutic approaches have been tested to overcome these symptoms, there is currently no standardized treatment for CIPN. According to current guidelines, Duloxetine is the only recommended agent for painful neuropathic symptoms. Therefore, finding effective therapies for CIPN is mandatory. The aim of this review was to dissect CIPN, the target and immunotherapy-based approaches to this disorder, as well as to offer new insights for new therapeutic perspectives., (Copyright © 2022 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background: Unplanned hospital readmissions (HRAs) are very common in cancer patients. These events can potentially impair the patients' health-related quality of life and increase cancer care costs. In this study, data-driven prediction models were developed for identifying patients at a higher risk for HRA., Methods: A large dataset on cancer pain and additional data from clinical registries were used for conducting a Bayesian network analysis. A cohort of gastrointestinal cancer patients was selected. Logical and clinical relationships were a priori established to define and associate the considered variables including cancer type, body mass index (BMI), bone metastasis, serum albumin, nutritional support, breakthrough cancer pain (BTcP), and radiotherapy., Results: The best model (Bayesian Information Criterion) demonstrated that, in the investigated setting, unplanned HRAs are directly related to nutritional support ( p = 0.05) and radiotherapy. On the contrary, BTcP did not significantly affect HRAs. Nevertheless, the correlation between variables showed that when BMI ≥ 25 kg/m 2 , the spontaneous BTcP is more predictive for HRAs., Conclusions: Whilst not without limitations, a Bayesian model, combined with a careful selection of clinical variables, can represent a valid strategy for predicting unexpected HRA events in cancer patients. These findings could be useful for calibrating care interventions and implementing processes of resource allocation.

Background: The most effective strategy for managing cancer pain remotely should be better defined. There is a need to identify those patients who require increased attention and calibrated follow-up programs. Methods: Machine learning (ML) models were developed using the data prospectively obtained from a single-center program of telemedicine-based cancer pain management. These models included random forest (RF), gradient boosting machine (GBM), artificial neural network (ANN), and the LASSO−RIDGE algorithm. Thirteen demographic, social, clinical, and therapeutic variables were adopted to define the conditions that can affect the number of teleconsultations. After ML validation, the risk analysis for more than one remote consultation was assessed in target individuals. Results: The data from 158 patients were collected. In the training set, the accuracy was about 95% and 98% for ANN and RF, respectively. Nevertheless, the best accuracy on the test set was obtained with RF (70%). The ML-based simulations showed that young age (<55 years), lung cancer, and occurrence of breakthrough cancer pain help to predict the number of remote consultations. Elderly patients (>75 years) with bone metastases may require more telemedicine-based clinical evaluations. Conclusion: ML-based analyses may enable clinicians to identify the best model for predicting the need for more remote consultations. It could be useful for calibrating care interventions and resource allocation.

In the United States, from 1999 to 2019, opioid overdose, either regularly prescribed or illegally acquired, was the cause of death for nearly 500,000 people. In addition to this pronounced mortality burden that has increased gradually over time, opioid overdose has significant morbidity with severe risks and side effects. As a result, opioid misuse is a cause for concern and is considered an epidemic. This article examines the trends and consequences of the opioid epidemic presented in recent international literature, reflecting on the causes of this phenomenon and the possible strategies to address it. The detailed analysis of 33 international articles highlights numerous impacts in the social, public health, economic, and political spheres. The prescription opioid epidemic is an almost exclusively North American problem. This phenomenon should be carefully evaluated from a healthcare systems perspective, for consequential risks and harms of aggressive opioid prescription practices for pain management. Appropriate policies are required to manage opioid use and prevent abuse efficiently. Examples of proper policies vary, such as the use of validated questionnaires for the early identification of patients at risk of addiction, the effective use of regional and national prescription monitoring programs, and the proper dissemination and translation of knowledge to highlight the risks of prescription opioid abuse.

Background and Objectives: Proper breakthrough cancer pain (BTcP) management is of pivotal importance. Although rapid-acting, oral and nasal transmucosal, fentanyl formulations (rapid-onset opioids, ROOs) are licensed for BTcP treatment, not all guidelines recommend their use. Presumably, some research gaps need to be bridged to produce solid evidence. We present a bibliometric network analysis on ROOs for BTcP treatment., Methods: Documents were retrieved from the Web of Science (WOS) online database. The string was "rapid onset opioids" or "transmucosal fentanyl" and "breakthrough cancer pain". Year of publication, journal metrics (impact factor and quartile), title, document type, topic, and clinical setting (in-patients, outpatients, and palliative care) were extracted. The software tool VOSviewer (version 1.6.17) was used to analyze the semantic network analyzes, bibliographic coupling, journals analysis, and research networks., Results: 502 articles were found in WOS. A declining trend in published articles from 2014 to 2021 was observed. Approximately 50% of documents regard top quartile (Q1) journals. Most articles focused on ROOs efficacy, but abuse and misuse issues are poorly addressed. With respect to article type, we calculated 132 clinical investigations. The semantic network analysis found interconnections between the terms "breakthrough cancer pain," "opioids," and "cancers." The top co-cited article was published in 2000 and addressed pain assessment. The largest number of partnerships regarded the United States, Italy, and England., Conclusion: In this research area, most articles are published in top-ranked journals. Nevertheless, paramount topics should be better addressed, and the implementation of research networks is needed., (Copyright © 2022 American Academy of Hospice and Palliative Medicine. Published by Elsevier Inc. All rights reserved.)

SARS-CoV-2 infection can impact the physical, cognitive, mental health of patients, especially in those recovered in intensive care units. Moreover, it was proved that the effects of the virus may persist for weeks or months. The term long-COVID or post-COVID syndrome is commonly used for indicating a variety of physical and psychological symptoms that continue after the resolution of the acute phase. This narrative review is aimed at providing an updated overview of the impact of physical, cognitive, and psychological health disorders in COVID-19 survivors, by summarizing the data already published in literature in the last year. Studies cited were found through PubMed searches. We also presented an overview of the post-COVID-19 health consequences on three important aspects: nutritional status, neurological disorders, and physical health. Moreover, to activate a correct health planning policy, a multidisciplinary approach for addressing the post- COVID-19 issue, has been proposed. Finally, the involvement of health professionals is necessary even after the pandemic, to reduce expected post-pandemic psychosocial responses and mental health disorders., (© 2021. The Author(s).)

Triple-Negative Breast Cancer (TNBC), represents a subtype of breast cancer in which the estrogens receptor (ER) negative, the progesterone receptor (PR) negative and the human epidermal growth factor receptor 2 (HER2) negative, are not expressed. Thusly, TNBC does not respond to hormonal therapies or to those targeting the HER2 protein receptors. To overcome this flawed issue, new alternative therapies based on the use of natural substances, as the (-) - epigallocatechin 3-gallate (EGCG), has been proposed. It is largely documented that EGCG, the principal constituent of green tea, has suppressive effects on different types of cancer, including breast cancer, through the regulation of different signaling pathways. Thus, is reasonable to assume that EGCG could be viewed as a therapeutic option for the prevention and the treatment of TNBC. Here, we summarizing these promising results with the scope of turn a light on the potential roles of EGCG in the treatment of TNBC patients., Competing Interests: Competing interestsThe authors declare that they have no competing interests., (© The Author(s). 2020.)

Rationale: Robot-assisted laparoscopic prostatectomy (RALP) is the most frequent strategy used for the surgical remedy of patients with localized prostate cancer. Although there is awareness about potential patient positioning nerve injuries, iatrogenic nerve lesions are less described in the literature. Here, we report 3 cases of patients who presented with neuropathic painful complications due to RALP-associated nerve lesions., Patient Concerns: A 62-year-old patient (case 1), a 72-year-old male (case 2), and a 57-year-old patient (case 3) presented at the clinic with symptoms of neuropathic pain after RALP surgery., Diagnosis: Patients were diagnosed with a potential injury of different branches of the pudendal nerve (cases 1 and 2), and left obturator nerve (case 3)., Interventions: Patients underwent multimodal pharmacologic treatment through pregabalin, weak opioids, strong opioid, paracetamol, and adjuvants. In cases 2 and 3, a multidisciplinary approach was needed. As the patients responded to conservative treatment, invasive approaches were not necessary., Outcomes: After treatment, the patients of case 1 showed pain relief after 4 days, paresthesia resolved in 15 days, whereas the anal crushing sensation lasted for approximately 1 month. In case 2, after 4 weeks of treatment, the patient experienced a considerable decrement in pain intensity with complete response after 4 months. In case 3, pain relief was achieved after 2 days, motor symptoms recovery after 2 weeks, and neuropathic features resolved completely after 5 weeks although the obturator sign resolved within 2 months., Lessons: The RALP-associated neurologic injuries may occur even when performed by highly experienced surgeons. A better understanding of the potential iatrogenic nerve lesions can surely allow an improvement in the surgical technique. A multidisciplinary approach and early multimodal pain strategy are mandatory for managing these complications.

Background: An "epidemic use" of legal opioids in the USA and other countries has been reported in the last 15 years. We have analysed the database of the Italian Ministry of Health regarding the prescription of opioids for pain management to verify the trend of opioids uses in Italy., Methods: The amount of opioids prescribed for every single Italian patient in 2013 was anonymously recorded and transformed in daily MED (morphine equivalent dose). We considered every monthly percentage increase of MED during the entire period of chronic therapy for each patient., Results: Classes of dosage increase for all patients in chronic therapy, distinguished between cancer and non-cancer ones, were created. We deduce that decreases or increases of small proportions prevailed in the observation period., Conclusions: The opioids "plague" that is striking the USA is not registered in Italy during the observation period. The reasons might be due to the innovative and effective law 38/2010 and a health care system able to guarantee appropriate prescriptions for major analgesics.

Human pancreatic cancer is one of the leading causes of mortality and morbidity worldwide. Despite surgical resection remains the only curative therapeutic treatment for this disease, only the minority of patients can be resected due to late diagnosis. Recently, new chemotherapy schemes with the combination of different drugs have been shown to improve disease-free survival, although best results were obtained mostly as neoadjuvant chemotherapy in the minority of patients with resectable tumor. Consequently, there is stimulated interest in new chemotherapeutic approaches and alternative medicines. Several studies showed that the use of natural compounds, such as phytochemicals, represents a promising strategy for pancreatic cancer treatment. One popular phytochemical with great anticancer properties, is the (-)-epigallocate-chin3-O-gallate (EGCG), the most abundant catechin found in green tea. Accumulating evidences demonstrated that EGCG induces apoptosis and inhibits tumor progression by modulating different signaling pathways in pancreatic cancer. For these encouraging results, this catechin is currently used in clinical trials for treatment of various type of cancer and other diseases, although its poor bioavailability and poor stability represent severe limitations. Therefore, many researchers tried to develop a new strategy based of the use of nanotechnology which increases EGCG stability and bioavailability and simultaneously targets cancer cells in order to improve its anti-tumor effects. The aim of this article is to dissect the use of EGCG for management of pancreatic cancer, by reviewing the pre-clinical studies reported in literature.

Objective: The aim of this study was to prospectively assess the efficacy and safety of low doses of sublingual fentanyl (SLF) for the treatment of breakthrough pain (BTP) in cancer patients in patients who were receiving low opioid doses for background analgesia., Methods: A sample of cancer patients presenting BTP episodes and receiving stable low doses of opioids for background pain (less than 60 mg of oral morphine equivalents) was selected to assess the efficacy and safety of low doses of SLF (67 μg). For each patient, data from four consecutive episodes were collected. For each episode, changes in pain intensity and adverse effects when pain got severe (T0), and 5, 10, and 15 min after SLF administration (T5-T30) were recorded. The occurrence of serious effects occurring within 2 h of SLF administration were also considered., Results: Fifty-one patients were recruited for the study. The mean age was 66.8 (SD 12.9). A mean of 3.3 episodes/patient were recorded. Four patients did not have episodes of BTP. 147 episodes were evaluated. Six episodes (4.1 %) required a rescue medication at T30. Pain intensity significantly decreased at T5, T10, T15 and T30 (p < 0.0005 in all cases). A high percentage of patients had a pain reduction of more than 33 and 50 % at T5, T10, T15 and T30. Adverse effects were mild and generally already present, due to basal opioid treatment or disease. No serious adverse effects were observed for the subsequent 2 h., Conclusion: This study suggests that SLF given in low doses in patients receiving lower doses of opioids for background analgesia is safe and effective in clinical practice.

Introduction: An ongoing national multicenter survey [Italian Oncologic Pain multiSetting Multicentric Survey (IOPS-MS)] is evaluating the characteristics of breakthrough cancer pain (BTP) in different clinical settings. Preliminary data from the first 1500 cancer patients with BTP enrolled in this study are presented here., Methods: Thirty-two clinical centers are involved in the survey. A diagnosis of BTP was performed by a standard algorithm. Epidemiological data, Karnofsky index, stage of disease, presence and sites of metastases, ongoing oncologic treatment, and characteristics of background pain and BTP and their treatments were recorded. Background pain and BTP intensity were measured. Patients were also questioned about BTP predictability, BTP onset (≤10 or >10 min), BTP duration, background and BTP medications and their doses, time to meaningful pain relief after BTP medication, and satisfaction with BTP medication. The occurrence of adverse reactions was also assessed, as well as mucosal toxicity., Results: Background pain was well controlled with opioid treatment (numerical rating scale 3.0 ± 1.1). Patients reported 2.5 ± 1.6 BTP episodes/day with a mean intensity of 7.5 ± 1.4 and duration of 43 ± 40 min; 977 patients (65.1%) reported non-predictable BTP, and 1076 patients (71.7%) reported a rapid onset of BTP (≤10 min). Higher patient satisfaction was reported by patients treated with fast onset opioids., Conclusions: These preliminary data underline that the standard algorithm used is a valid tool for a proper diagnosis of BTP in cancer patients. Moreover, rapid relief of pain is crucial for patients' satisfaction. The final IOPS-MS data are necessary to understand relationships between BTP characteristics and other clinical variables in oncologic patients., Funding: Molteni Farmaceutici, Italy.

Individually tailored pharmacological regimen is the standard approach for treating patients affected by cancer pain, allowing the control of symptoms in approximately 90% of cases. If this strategy is ineffective it is possible to use more complex invasive, or minimally invasive, techniques. Nevertheless, both patients and health care professionals often underestimate the impact of cancer pain on psychological distress, and do not consider the potential benefits of psychological treatments to help manage cancer pain. These non-pharmacological strategies should be part of the multidisciplinary pain therapy, supporting and strengthening drug therapy. The purpose of this brief commentary is to discuss the role of psychological and rehabilitation approaches for improving the quality of life and the psychosocial outcomes in patients with cancer pain.

The term "breakthrough cancer pain" (BTcP) was introduced about 25 years ago. Peaks of pain intensity reported in patients with cancer had been invariably examined in the past years, providing relevant information for a better knowledge of this phenomenon and its treatment. The aim of this critical review was to provide the golden rules, namely, the 10 commandments, for a correct diagnostic pathway of BTcP and a consequent personalized pharmacological treatment. These are as follows: 1) assessment of background analgesia, 2) drugs used for background analgesia, 3) BTcP is a frequent phenomenon, 4) characteristics of BTcP, 5) diagnosis of BTcP, 6) continuous assessment, 7) tailored pharmacological treatment of BTcP, 8) selection of BTcP medication, 9) dosing BTcP medications, and 10) education. These steps may help clinicians to recognize and treat BTcP adequately., (Copyright © 2016 International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Published by Elsevier Inc. All rights reserved.)

Although we describe a clinical situation that most likely occurs in hundreds of operatory rooms in the world, we report this case as provocation. It concerns an unexpected awakening from an appropriate depth of anesthesia, although the BIS monitor showed a BIS index of less than 50 for a prolonged period before and after the event. Approximately 30 min after induction of anesthesia, the patient had a hypothetic sudden arousal of consciousness, with spontaneous movements, facial muscle activation, intolerance to the tracheal tube, and tearing. After immediate intravenous administration of midazolam (4 mg), the patient returned to a depth of anesthesia status, and surgery was completed uneventfully. The patient had no recall of the event when questioned during the episode, at emergence, or at 24 h, 36 h, and 7 days after surgery. Were these events spinal reflexes to pain or stimulation although the cortex was still anesthetized? Maybe this is the more rational explanation. Was the patient awake but not aware? Is it possible that our patient experienced only a transient arousal from consciousness, and that he did not have recall because the arousal time was short and we blocked memory consolidation? The latter hypothesis provides an opportunity to discuss the evidence that at the moment there is no device to assess the depth of anesthesia. We also focus on the possibility of interfering with memory processing under anesthesia.

Controversies exist about the definition and epidemiology of breakthrough cancer pain (BTcP), the pharmacological treatment options, drug dosing, and how to select the medications for BTcP among the new fentanyl products. Existing data were critically evaluated to provide recommendations by an expert group. An algorithm to diagnose BTcP should be used followed by a careful assessment. Fentanyl products provide efficacy and rapidity of action to counteract the temporal pattern of BTcP. The doses of opioids used for background pain should guide the choice of the doses of fentanyl products. The choice of fentanyl products should be based on individual clinical conditions.

Context: Fentanyl products have shown superiority to oral opioids for the management of breakthrough cancer pain (BTcP). However, these studies did not use appropriate patient selection, and drugs have been compared by using different rationales., Objectives: The aim of this randomized, crossover, controlled study was to compare efficacy and safety of fentanyl buccal tablets (FBTs) and oral morphine (OM), given in doses proportional to opioid daily doses., Methods: Cancer patients with pain receiving ≥60 mg or more of oral morphine equivalents per day and presenting with ≤3 episodes of BTcP per day were included. In a randomized, crossover manner, patients received FBT or OM at doses proportional to the daily opioid regimen in four consecutive episodes of BTcP. Pain intensity was measured before (T0) and 15 (T15) and 30 minutes (T30), after study drugs., Results: In total, 263 episodes of BTcP were treated. A statistical difference in changes in pain intensity-decrease of ≥33% and ≥50%-between the two groups was observed at T15 and T30 (P < 0.0005). No severe adverse effects after study drug administration were observed., Conclusion: When used in doses proportional to the basal opioid regimen, FBT showed a clear superiority and was well tolerated when compared with OM during the first 30 minutes, which is the approximate target for a timely intervention required for a BTcP medication., (Copyright © 2015 American Academy of Hospice and Palliative Medicine. Published by Elsevier Inc. All rights reserved.)

Background: Uniportal video-assisted thoracic surgery (VATS) technique has been described both for diagnostic and therapeutic indications. Outcomes after uniportal VATS have never been reported in large series., Methods: Between January 2000 and December 2010, 644 uniportal VATS procedures (334 male and 310 female patients; median age, 55.5 years; range, 16 to 85) were performed by a single surgeon. This figure represents 27.7% of all the thoracic surgical procedures in the study period (2,369). Of the 644 uniportal VATS, 329 (51.1%) were diagnostic procedures for pleural conditions. Of the remaining 315 uniportal VATS procedures, 14 (2.2%) were performed for pre-thoracotomy exploration for lung cancer, and 115 (17.8%) for miscellaneous conditions including diagnosis of mediastinal masses. In addition, 186 nonanatomic wedge resections (28.9% of the total uniportal VATS procedures) were performed for pulmonary conditions; of these, 146 were done for pulmonary nodules., Results: Median operative time was 18 and 22 minutes for uniportal VATS for diagnostic non-pulmonary indications and for wedge resections, respectively. Out of 644 patients, conversion to either 2 or 3 port VATS or minithoracotomy was necessary in 3.7% of the patients, often due to incomplete lung collapse (92%). Inclusive of the day of insertion, the chest drain was removed after a median of 4.3 (range, 2 to 20) and 2.4 days (range, 0 to 6) after uniportal VATS for pleural effusions and uniportal VATS lung wedge resections, respectively. Mortality and major morbidity after uniportal VATS was 0.6% and 2.8%, respectively. All deaths reported after uniportal VATS were for pleural effusions. Inclusive of the operative day, median hospitalization after surgery for uniportal VATS for pleural effusions and for wedge resections were 5.3 and 3.4 days, respectively., Conclusions: In our experience, uniportal VATS was performed in one third of our surgical candidates with limited operative time, a very low conversion rate to conventional VATS or minithoracotomy, a very low morbidity and mortality, and, short hospitalization. Uniportal VATS is an underappreciated procedure that can be reliably used in the diagnostic pathways of several intrathoracic conditions and to resect small pulmonary nodules with either diagnostic or therapeutic purposes. As such, uniportal VATS represents a consolidated addition to the surgical armamentarium., (Copyright © 2013 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)