The Italian Experience in the Development of Mesothelioma Registries: A Pathway for Other Countries to Address the Negative Legacy of Asbestos.

Asbestos (all forms, including chrysotile, crocidolite, amosite, tremolite, actinolite, and anthophyllite) is carcinogenic to humans and causally associated with mesothelioma and cancer of the lung, larynx, and ovary. It is one of the carcinogens most diffuse in the world, in workplaces, but also in the environment and is responsible for a very high global cancer burden. A large number of countries, mostly with high-income economies, has banned the use of asbestos which, however, is still widespread in low- and middle-income countries. It remains, thus, one of the most common occupational and environmental carcinogens worldwide. Italy issued an asbestos ban in 1992, following the dramatic observation of a large increase in mortality from mesothelioma and other asbestos-related diseases in exposed workers and also in subjects with non-occupational exposure. A mesothelioma registry was also organized and still monitors the occurrence of mesothelioma cases, conducting a case-by-case evaluation of asbestos exposure. In this report, we describe two Italian communities, Casale Monferrato and Broni, that faced an epidemic of mesothelioma resulting from the production of asbestos cement and the diffuse environmental exposure; we present the activity and results of the Italian mesothelioma registry (ReNaM), describe the risk-communication activities at the local and national level with a focus on international cooperation and also describe the interaction between mesothelioma registration and medical services specialized in mesothelioma diagnosis and treatment in an area at high risk of mesothelioma. Finally, we assess the potential application of the solutions and methods already developed in Italy in a city in Colombia with high mesothelioma incidence associated with the production of asbestos-cement materials and the presence of diffuse environmental asbestos pollution.

Breakthrough Cancer Pain Clinical Features and Differential Opioids Response: A Machine Learning Approach in Patients With Cancer From the IOPS-MS Study.

PURPOSE: A large proportion of patients with cancer suffer from breakthrough cancer pain (BTcP). Several unmet clinical needs concerning BTcP treatment, such as optimal opioid dosages, are being investigated. In this analysis the hypothesis, we explore with an unsupervised learning algorithm whether distinct subtypes of BTcP exist and whether they can provide new insights into clinical practice. METHODS: Partitioning around a k-medoids algorithm on a large data set of patients with BTcP, previously collected by the Italian Oncologic Pain Survey group, was used to identify possible subgroups of BTcP. Resulting clusters were analyzed in terms of BTcP therapy satisfaction, clinical features, and use of basal pain and rapid-onset opioids. Opioid dosages were converted to a unique scale and the BTcP opioids-to-basal pain opioids ratio was calculated for each patient. We used polynomial logistic regression to catch nonlinear relationships between therapy satisfaction and opioid use. RESULTS: Our algorithm identified 12 distinct BTcP clusters. Optimal BTcP opioids-to-basal pain opioids ratios differed across the clusters, ranging from 15% to 50%. The majority of clusters were linked to a peculiar association of certain drugs with therapy satisfaction or dissatisfaction. A free online tool was created for new patients' cluster computation to validate these clusters in future studies and provide handy indications for personalized BTcP therapy. CONCLUSION: This work proposes a classification for BTcP and identifies subgroups of patients with unique efficacy of different pain medications. This work supports the theory that the optimal dose of BTcP opioids depends on the dose of basal opioids and identifies novel values that are possibly useful for future trials. These results will allow us to target BTcP therapy on the basis of patient characteristics and to define a precision medicine strategy also for supportive care.

Factors Influencing the Clinical Presentation of Breakthrough Pain in Cancer Patients.

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.

Breakthrough Cancer Pain: Preliminary Data of The Italian Oncologic Pain Multisetting Multicentric Survey (IOPS-MS).

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.

Symptom burden in mesothelioma patients admitted to home palliative care.

CONTEXT: Mesothelioma is a very aggressive cancer that is brought on by asbestos exposure. Because there is a long latency period between exposure to asbestos and symptoms of disease, most patients with mesothelioma present with advanced disease and survive an average of 8-12 months. Thus, best supportive care should be considered critical to optimally manage these patients. AIM: The aim of this study was to examine the epidemiological characteristics and symptom burden of mesothelioma patients when admitted to home palliative care. METHODS: The charts of a consecutive sample of patients admitted to the home palliative care program with a diagnosis of mesothelioma in an endemic industrialized area were reviewed. The estimated survival time was about two months from admission. Epidemiological characteristics were collected. Karnofsky status, characteristics of pain and analgesic treatment at time of admission were recorded. ESAS (Edmonton Symptom Assessment System) and other clinical problems reported in the charts at admission time were also recorded. RESULTS: Of the 674 charts reviewed, 56 patients (8.3%) had a diagnosis of mesothelioma. About three quarters of those had pain, with 18 and 2 patients with moderate and severe pain, respectively, despite receiving medium to high doses of opioids. The principal pain site was the chest. Pain was significantly associated with opioid consumption (p < .0005) and dyspnea (p = .049). Symptom burden was relevant, with a global ESAS of about 40. Pain, weakness, poor appetite, poor well-being, and dyspnea were the most frequent symptoms with the highest intensity; cough and pleural effusion were more frequently present as clinical problems. CONCLUSION: This study shows that mesothelioma is a devastating cancer with a relevant symptom burden, and that patients were referred to palliative care late in the course of their disease, suggesting that earlier integration of palliative care should be considered to relieve suffering in all disease stages - not only at the end of life.

Asbestos fibers in the gallbladder of patients affected by benign biliary tract diseases.

PURPOSE: This exploratory study aimed to evaluate the presence of asbestos fibers in the biliary tract of patients living in an asbestos-polluted area using scanning electron microscopy. METHODS: Thin gallbladder sections were obtained from five patients who were operated on for gallbladder stones and the bile fluid of one of the patients was analyzed using variable-pressure scanning electron microscopy coupled with energy-dispersive spectroscopy. All patients were from Casale Monferrato, Italy, a well-known asbestos-polluted city, where the Eternit factory had operated since the beginning of the century until 1985. RESULTS: All the inorganic phases found in the gallbladder were analyzed for morphology and chemistry. Fibers and particles consistent with minerals defined by law as 'asbestos' were detected in three out of five patients. CONCLUSION: These findings suggest that asbestos fibers can be found in the gallbladder of patients exposed to asbestos, although how they reach the biliary tract remains unknown. Further studies to confirm these results are under way.

Asbestos in Italy.

Asbestos-related diseases remain common in Italy due to past exposures that were tolerated by a government distracted and manipulated by multinational asbestos corporations. The incidence of asbestos-related cancers has taken on almost epidemic proportions, for example, in Casale Monferrato in northwest Italy, where Eternit remained in operation until 1985, and in Monfalcone in northeast Italy, where naval dockyards and related activities created pollution. Authorities took action only after public protests, trade union pressures, and campaigning by the families of victims. Now that a ban exists in Italy, it is vital that it be fully enforced to reverse the epidemic of mesothelioma, lung cancer, and other asbestos-related diseases.