Lipocalin 2 increases after high-intensity exercise in humans and influences muscle gene expression and differentiation in mice.

Lipocalin 2 (LCN2) is an adipokine that accomplishes several functions in diverse organs. However, its importance in muscle and physical exercise is currently unknown. We observed that following acute high-intensity exercise ("Gran Sasso d'Italia" vertical run), LCN2 serum levels were increased. The Wnt pathway antagonist, DKK1, was also increased after the run, positively correlating with LCN2, and the same was found for the cytokine Interleukin 6. We, therefore, investigated the involvement of LCN2 in muscle physiology employing an Lcn2 global knockout (Lcn2-/- ) mouse model. Lcn2-/- mice presented with smaller muscle fibres but normal muscle performance (grip strength metre) and muscle weight. At variance with wild type (WT) mice, the inflammatory cytokine Interleukin 6 was undetectable in Lcn2-/- mice at all ages. Intriguingly, Lcn2-/- mice did not lose gastrocnemius and quadriceps muscle mass and muscle performance following hindlimb suspension, while at variance with WT, they lose soleus muscle mass. In vitro, LCN2 treatment reduced the myogenic differentiation of C2C12 and primary mouse myoblasts and influenced their gene expression. Treating myoblasts with LCN2 reduced myogenesis, suggesting that LCN2 may negatively affect muscle physiology when upregulated following high-intensity exercise.

Financial distress and its impact on symptom expression in advanced cancer patients.

AIM: To assess financial distress (FD) and its impact on symptom expression and other quality of life issues PATIENTS AND METHODS: Advanced cancer patients admitted to inpatient and outpatient clinics were selected. Standard epidemiological data including age, gender, primary cancer diagnosis, and Karnofsky level were recorded. Data regarding marital status, number of cohabitants, religious belief, educational level, and family income (< 1000, 1000-3.000, > 3000 euros), as well as extra costs not covered by health care system, were collected. Symptom burden including FD was measured by Edmonton Symptom Assessment Scale (ESAS), FACT-G (Functional Assessment of Cancer Therapy-General), and HADS (Hospital Anxiety Depression scale) were measured. RESULTS: Two hundred thirty-six patients were evaluated. The mean FD was 3.55 (SD 3.1). One hundred patients (42%) had a FD of ≥ 4. There was an inverse correlation between FD and income (P = 0.032). Most patients incurred in extra-costs, the most frequent being for drugs (n, 114). FD was inversely associated with age (P = 0.024), marital status (divorced or separated, P = 0.005), ESAS anxiety (P = 0.006), total ESAS (P = 0.019), physical well-being (P = 0.033), poor social family well-being (P = 0.004), emotional well-being (P = 0.045), poor functional well-being (P = 0.019), HADS-A (P = 0.003), and global HADS (P = 0.034). Family income was inversely related to age (P = 0.023), education level (P < 0.0005), less number of hospital admissions in the last month (P = 0.020), physical well-being (P = 0.039), social/family well-being (P = 0.020), and total well-being (P = 0.001). CONCLUSION: FD is very common in advanced cancer patients. FD was associated with anxiety, depression, and poor quality of life. The screening of FD may allow to develop effective interventions of social support.

The lower the expectations in controlling the symptoms of advanced cancer patients, the better the clinical response.

AIM: The aim of this study was to compare patients' global impression (PGI) and the achievement of personalised symptom goal response (PSGR), after a comprehensive palliative care treatment in advanced cancer patients having high (HPSG) and low symptom goals (LPSG). PATIENTS AND METHODS: Advanced cancer patients admitted to palliative care units rated symptoms intensity by the Edmonton Symptom Assessment Score (ESAS) at admission and then after one week of comprehensive palliative care treatment. For each symptom, patients were divided into two groups, according to their patient symptom goal (PSG): ≥4 (HPSG), and 0-2 (LPSG). PGI and PSGR were evaluated after one week of palliative care. The Memorial Delirium Assessment Scale (MDAS) was assessed at admission. RESULTS: After one week of palliative care, changes in ESAS items were significantly larger in the HPSG group. HPSG patients had a better PGI and reached their target more frequently than LPSG patients for pain, weakness, and poor well-being. LPSG patients were more likely to obtain their target for appetite and insomnia. HPSG patients were more likely to have a lower Karnofsky, a lower educational level, older age, or higher MDAS values for the different ESAS items. CONCLUSION: Advanced cancer patients with low expectations (HPSG) were more likely to achieve their PSGR after a comprehensive palliative care treatment, reporting also a better PGI for some leading symptoms such as pain, weakness, and poor well-being. More fragile patients seem to have lower expectations and to be more likely to be satisfied.

Breakthrough Cancer Pain in Patients Receiving Low Doses of Opioids for Background Pain.

BACKGROUND: This study aimed to assess the characteristics of breakthrough cancer pain (BTcP) in patients receiving low doses of opioids for background pain in comparison with patients receiving at least 60 mg of oral morphine equivalents (OME). MATERIALS AND METHODS: Patients with advanced cancer receiving less than 60 mg/day of OME with episodes of BTcP were included in the analysis (group L). Data were compared with patients receiving doses of opioids ≥60 mg of OME (group H). Pain intensity, current analgesic therapy, number of BTcP episodes, intensity of BTcP, its predictability and triggers, onset duration, interference with daily activities, BTcP medications, and time to meaningful pain relief were collected. Adverse effects imputable to a BTcP medication were recorded. RESULTS: A total of 1,418 and 2,474 patients were included in groups L and H, respectively. A lower number of BTcP episodes (p = .005), a lower BTcP intensity (p = .0001), a faster BTcP onset (p = .024), and a longer time to meaningful pain relief after taking a BTcP medication (p = .009) were found in group L as compared with group H. In group L, BTcP interference on daily activity was less than in group H (p = .009). Patients in group L were less likely to be prescribed an opioid as BTcP medication in comparison with patients in group H (p = .0001). Opioid doses used for BTcP were significantly higher in group H. Patients in group L were more likely to be less satisfied (p = .003) than patients in group H. No adverse effects of severe intensity were reported in both groups. CONCLUSION: Patients receiving lower doses of opioids exhibit some differences in BTcP presentation: fewer episodes with lower intensity and a faster onset, a longer time to meaningful pain relief, and less satisfaction with BTcP medication. A relevant percentage of patients was receiving fentanyl preparations normally reserved for patients receiving higher doses of opioids. IMPLICATIONS FOR PRACTICE: Breakthrough pain is present in patients receiving low doses of opioids. It has its own peculiarities: less frequent, lower intensity, faster onset, longer time to meaningful pain relief, and less satisfaction with medication. Many patients were prescribed fentanyl preparations, which are normally reserved for patients receiving higher doses of opioids.

Personalized goal for insomnia and clinical response in advanced cancer patients.

AIM: The aim of this study was to assess the Personalized Insomnia Intensity Goal (PIIG), the achievement of Personalized Goal Response (PGR), and Patient Global Impression (PGI) after a comprehensive symptom management. PATIENTS AND METHODS: Advanced cancer patients admitted to palliative care units rated pain and symptoms intensity and their PIIG by using the Edmonton Symptom Assessment Score (ESAS) (T0). In patients with significant levels of insomnia, the achievement of target expected (PIIG) was measured (patient goal response, PIGR), as well the patient global impression (PGI), by the minimal clinically important difference (MCID), after a comprehensive symptom management (T7). RESULTS: Three hundred ninety-seven patients with a level of insomnia of ≥ 3 on ESAS were analyzed in this study. The mean values of PIIG at T0 and T7 were 1.2 (SD 1.5) and 0.9 (SD 1.4), respectively. Most patients (n = 406, 89.8%) indicated a PIIG of ≤ 3 as a target at T0. Such target was significantly lower at T7 (p = < 0.0005). PGI, expressed as MCID, was perceived with a mean decrease in insomnia intensity of - 2.3. In a minority of patients (n = 26; 5.8%) insomnia worsened, with a MCID of 0.50 (SD 2.8). Higher insomnia intensity at T0 and lower insomnia intensity at T7 were independently related to PGI. PIGR was achieved in 87.9% of patients. PIGR was associated with PIIG at T0, and inversely associated to insomnia intensity at T0 and T7, and PIIG at T7. CONCLUSION: PGIR and PGI seem to be relevant for evaluating the effects of a comprehensive management of insomnia, suggesting therapeutic decisions according to PIIG. Some factors influencing the individual target and clinical response have been detected.

Personalized Pain Goals and Responses in Advanced Cancer Patients.

OBJECTIVE: To assess the personalized pain intensity goal (PPIG), the achievement of a personalized pain goal response (PPGR), and patients' global impression (PGI) in advanced cancer patients after a comprehensive pain and symptom management. DESIGN: Prospective, longitudinal. SETTING: Acute pain relief and palliative/supportive care. SUBJECTS: 689 advanced cancer patients. METHODS: Measurement of Edmonton Symptom Assessment Score (ESAS) and personalized pain intensity goal (PPIG) at admission (T0). After a week (T7) personalized pain goal response (PPGR) and patients' global impression (PGI) were evaluated. RESULTS: The mean PPIG was 1.33 (SD 1.59). A mean decrease in pain intensity of - 2.09 was required on PPIG to perceive a minimal clinically important difference (MCID). A better improvement corresponded to a mean change of - 3.41 points, while a much better improvement corresponded to a mean of - 4.59 points. Patients perceived a MCID (little worse) with a mean increase in pain intensity of 0.25, and a worse with a mean increase of 2.33 points. Higher pain intensity at T0 and lower pain intensity at T7 were independently related to PGI. 207 (30.0%) patients achieved PPGR. PPGR was associated with higher PPIG at T0 and T7, and inversely associated to pain intensity at T0 and T7, and Karnofsky level. Patients with high pain intensity at T0 achieved a favorable PGI, even when PPIG was not achieved by PPGR. CONCLUSION: PPIG, PPGR and PGI seem to be relevant for evaluating the effects of a comprehensive management of pain, assisting decision-making process according to patients' expectations. Some factors may be implicated in determining the individual target and the clinical response.

Personalized Symptom Goals and Patient Global Impression on Clinical Changes in Advanced Cancer Patients.

BACKGROUND: The aim of this study was to assess the patients' global impression (PGI) after symptom management, as well as the achievement of personalized symptom goals (PSG). The secondary outcome was to assess related factors. SUBJECTS, MATERIALS, AND METHODS: Advanced cancer patients admitted to palliative care units rated symptom intensity by using the Edmonton Symptom Assessment Score (ESAS) at admission and then after 1 week. For each symptom, patient-reported PGI and PSG, as well as the rate of PSG response, were evaluated. RESULTS: Eight hundred seventy-six patients were taken into consideration for this study. A mean of 1.71-2.16 points was necessary to perceive a bit better improvement of symptom intensity. Most patients had a PSG of ≤3. A statistically significant number of patients achieved their PSG after starting palliative care. Patients with high intensity of ESAS items at admission achieved a more favorable PGI response. In the multivariate analysis, symptom intensity and PSG were the most frequent factors independently associated to a best PGI, whereas high levels of Karnofsky had a lower odd ratio. CONCLUSION: PSG and PGI seem to be relevant for patients' assessment and decision-making process, translating in terms of therapeutic intervention. Some factors may be implicated in determining the individual target and clinical response. IMPLICATIONS FOR PRACTICE: Personalized symptom goals and global impression of change are relevant for patients' assessment and decision-making process, translating in terms of therapeutic intervention. Some factors may be implicated in determining the individual target and clinical response.

Opioid-induced bowel dysfunction: suggestions from a multidisciplinary expert Board.

Constipation, one of the adverse effects of opioid therapy with a major impact on quality of life, is still an unmet need for cancer patients, particularly those with an advanced and progressive disease, and for non-cancer patients chronically treated with opioids. The awareness of this condition is poor among healthcare providers, despite the recent publication of guidelines and consensus conferences. An early multidisciplinary approach of opioid-induced bowel dysfunction (OIBD), based on available therapies of proven effectiveness, could support clinicians in managing this condition, thus increasing patients' adherence to pain therapy. Several Italian experts involved in the management of patients suffering from pain (anaesthesia pain therapy, oncology, haematology, palliative care, gastroenterology) joined in a Board in order to draw up an expert opinion on OIBD. The most frequent and still unsolved issues in this field were examined, including a more comprehensive definition of OIBD, the benefits of early intervention to prevent its occurrence and the most appropriate use of peripherally acting mu-opioid receptor antagonists (PAMORAs). The use of the recently introduced PAMORA naloxegol was analysed, in light of the current literature. The Board proposed a solution for each open issue in the form of recommendations, integrated with the contribution of representatives from different disciplines and often accompanied by procedural algorithms immediately usable and applicable in daily clinical practice. Safety and quality of life of the patient suffering from pain and from the adverse effects of pain therapies have been the mainstays of this expert opinion, in cooperation with general practitioners and caregivers.

Bone Metastasis Pain, from the Bench to the Bedside.

Bone is the most frequent site of metastasis of the most common cancers in men and women. Bone metastasis incidence has been steadily increasing over the years, mainly because of higher life expectancy in oncologic patients. Although bone metastases are sometimes asymptomatic, their consequences are most often devastating, impairing both life quality and expectancy, due to the occurrence of the skeletal-related events, including bone fractures, hypercalcemia and spinal cord compression. Up to 75% of patients endure crippling cancer-induced bone pain (CIBP), against which we have very few weapons. This review's purpose is to discuss the molecular and cellular mechanisms that lead to CIBP, including how cancer cells convert the bone "virtuous cycle" into a cancer-fuelling "vicious cycle", and how this leads to the release of molecular mediators of pain, including protons, neurotrophins, interleukins, chemokines and ATP. Preclinical tests and assays to evaluate CIBP, including the incapacitance tester (in vivo), and neuron/glial activation in the dorsal root ganglia/spinal cord (ex vivo) will also be presented. Furthermore, current therapeutic options for CIBP are quite limited and nonspecific and they will also be discussed, along with up-and-coming options that may render CIBP easier to treat and let patients forget they are patients.

Prevalence of delirium in advanced cancer patients in home care and hospice and outcomes after 1 week of palliative care.

AIM: The aim of this study was to assess the prevalence of delirium in advanced cancer patients admitted to different palliative care services in Italy and possible related factors. The secondary outcome was to assess the changes of delirium after 1 week of palliative care. METHODS: A consecutive sample of patients was screened for delirium in period of 1 year in seven palliative care services. General data, including primary tumor, age, gender, concomitant disease, palliative prognostic score (PaP), and Karnofsky status, were collected. Possible causes or factors associated with delirium were looked for. The Edmonton Symptom Assessment Scale was used to assess physical and psychological symptoms and the Memorial Delirium Assessment Scale (MDAS) to assess the cognitive status of patients, at admission (T0) and 1 week after palliative care (T7). RESULTS: Of 848 patients screened, 263 patients were evaluated. Sixty-six patients had only the initial evaluation. The mean Karnofsky status was 34.1 (SD = 6.69); the mean PaP score at admission was 6.9 (SD = 3.97). The mean duration of palliative care assistance, equivalent to survival, was 38.4 days (SD = 48, range 2-220). The mean MDAS values at admission and after 1 week of palliative care were 6.9 (SD = 6.71) and 8.8 (SD = 8.26), respectively. One hundred ten patients (41.8%) and 167 patients (67.3%) had MDAS values ≥ 7 at admission and after 1 week of palliative care, respectively. Age, dehydration, cachexia, chemotherapy in the last three months, and intensity of drowsiness and dyspnea were independently associated with a MDAS > 7. A worsening of drowsiness, the use of opioids, and the use of corticosteroids were independently associated with changes of MDAS from T0 to T7. CONCLUSION: Although the prevalence of delirium seems to be similar to that reported in other acute settings, delirium tended to worsen or poorly responded to a palliative care treatment. Some clinical factors were independently associated with delirium. This information is relevant for decision-making when delirium does not change despite a traditional intervention. Continuous assessment of delirium should be performed in these settings to detect deterioration of cognitive function. Further studies should elucidate whether an earlier approach to palliative care would decrease the prevalence of delirium at a late stage of disease.

Attitudes of palliative home care physicians towards palliative sedation at home in Italy.

BACKGROUND: Information about the attitudes towards palliative sedation (PS) at home is limited. AIM: The aim of this survey was to assess the attitudes of palliative care physicians in Italy regarding PS at home. DESIGN: A questionnaire was submitted to a sample of palliative care physicians, asking information about their activity and attitudes towards PS at home. SETTING: This is a survey of home care physicians in Italy who were involved in end-of-life care decisions at home. RESULTS: One hundred and fifty participants responded. A large heterogeneity of home care organizations that generate some problems was found. Indications, intention and monitoring of PS seem to be appropriate, although some cultural and logistic conditions were limiting the use of PS. Specialized home care physicians are almost involved to start PS at home. Midazolam was seldom available at home and opioids were more frequently used. CONCLUSION: These data should prompt health care agencies to make a minimal set of drugs easily available for home care. Further research is necessary to compare attitudes in countries with different sociocultural profiles.

Sleep disturbances in advanced cancer patients admitted to a supportive/palliative care unit.

The aim of this study was to assess the prevalence of sleep disturbances and possible correlations with associated factors in a sample of patients admitted to an acute palliative/supportive care unit.A consecutive sample of patients with advanced cancer was prospectively assessed for a period of 6 months. Epidemiological and clinical data, treatments received in the last month, Karnofsky status, Edmonton Symptom Assessment System (ESAS), and concomitant medical treatment were also recorded. Patients were administered the Athens Insomnia Scale (AIS) and the Hospital Anxiety and depression scale (HADS).Two hundred nineteen patients met the inclusion criteria. The mean age was 65.4 years (SD 12.4), and 111 patients were males. The mean Karnofsky status was 46.6 (SD = 12). All patients had consistent sleep disturbances (AIS ≥6), with a large number of patients having intense-maximum sleep disturbances. No relationships of AIS with gender, age, primary diagnosis, socio-educational factors, and anticancer treatments were found. AIS score was significantly associated with Karnofsky; intensities of pain, asthenia, anorexia, anxiety, depression, drowsiness, and well-being; and the use of corticosteroids and benzodiazepines. There was a positive correlation of HADS anxiety and HADS depression with sleep disturbances (p = 0.000). In the multivariate analysis, AIS increased only with the level of anxiety and depression assessed by HADS.Sleep disturbances were ubiquitous in advanced cancer patients admitted to a supportive/palliative care unit and were strongly correlated with psychological distress. Assessment of sleep disorders is mandatory in this population for the obvious interference with quality of life.

The use of low doses of a sublingual fentanyl formulation for breakthrough pain in patients receiving low doses of opioids.

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.

Age differences in the last week of life in advanced cancer patients followed at home.

A retrospective analysis of a consecutive sample of patients admitted to a home care program was performed. Data were recorded in the last week through a backward analysis from the day before death as follows: 1 week before dying (-1W), 3 days before death (-3D), and the day before dying (-1D). Data to be collected included the Edmonton Symptom Assessment System (ESAS), background pain intensity, the prevalence of breakthrough pain, the use of opioids in the last week, and the need for palliative sedation, with indications, duration, and drugs used. Patients were distributed according to the following age ranges: adults (<65 years, A) and aged (≥65 years, O). Of the latter group, three subgroups were assessed: old (65-74 years, O1), very old (75-84 years, O2), and the oldest (≥85 years, O3). Four hundred eleven patients were assessed. At -W1, no statistical differences in intensity of ESAS items ≥4 among the age subgroups were found. For ESAS values at -1W, -3D, and -1D, no statistical differences were found unless for anorexia at -1W (p = 0.000) (more likely), depression at -3D (p = 0.000) (less likely), depression (p = 0.000), and dyspnea (p = 0.01) (less likely) at -1D in the oldest group (O3). No differences in pain intensity among the groups were found (p = 0.54). Opioid doses increased in time and were significantly lower in older patients (p = 0.000). The subcutaneous route was more frequently used at -3D and -1D in older patients. No differences in opioid switching were found among the groups (p = 0.56). Adult patients required more often palliative sedation (p = 0.003). Older patients have problems relatively similar to adult patients in the last week of life, unless for some symptoms. Older patients had also a lower opioid consumption, a more frequent use of the subcutaneous route, and a lower need for palliative sedation.

Prevalence of oral mucositis, dry mouth, and dysphagia in advanced cancer patients.

BACKGROUND: Oral symptoms can be a sign of an underlying systemic condition and have a significant impact on quality of life, nutrition, and cost of care, while these lesions are often studied in the context of cancer treatment. However, information regarding oral symptoms in advanced cancer patients is poor. The aim of this multicenter study was to determine the prevalence and the characteristics of oral symptoms in a large population of advanced cancer patients. METHODS: A consecutive sample of patients with advanced cancer for a period of 6 months was prospectively assessed for an observational study. At time of admission, the epidemiological characteristics, surgery-radiotherapy of head and neck, and oncologic treatments in the last month were recorded. The presence of mucositis, dry mouth, and dysphagia was assessed by clinical examination and patients' report and their intensity recorded. Patients were also asked whether they had limitation on nutrition of hydration due to the local condition. RESULTS: Six hundred sixty-nine patients were surveyed in the period taken into consideration. The mean age was 72.1 years (SD 12.3), and 342 patients were males. The primary tumors are listed in Table 1. The prevalence of mucositis was 22.3 %. The symptom relevantly reduced the ingestion of food or fluids and was statistically associated with the Karnofsky level and head and neck cancer. The prevalence of dry mouth was 40.4 %, with a mean intensity of 5.4 (SD 2.1). Several drugs were concomitantly given, particularly opioids (78 %), corticosteroids (75.3 %), and diuretics (70.2 %). Various and nonhomogeneous treatments were given for dry mouth, that was statistically associated with current or recent chemotherapy, and hematological tumors. The prevalence of dysphagia was 15.4 % with a mean intensity of 5.34 (SD 3). Dysphagia for liquids was observed in 52.4 % of cases. A high level of limitation for oral nutrition due to dysphagia was found, and in 53.4 % of patients, alternative routes to the oral one were used. Dysphagia was statistically associated with the Karnofsky level and head and neck cancer. A strong relationship between the three oral symptoms was found. CONCLUSION: In advanced cancer patients, a range of oral problems significantly may impact on the physical, social, and psychological well-being of advanced cancer patients to varying degrees. These symptoms should be carefully assessed early but become imperative in the palliative care setting when they produce relevant consequences that may be life-threatening other than limiting the daily activities, particularly eating and drinking.

Pain intensity as prognostic factor in cancer pain management.

AIM: The aim of this study was to prospectively assess the prognostic value of initial pain intensity and its duration in advanced cancer patients. METHODS: A prospective study was conducted in a sample of patients with cancer requiring pain control. Patients underwent standard analgesic strategies used in our palliative care units. Pain intensity was measured at admission (T0) and after successful dose titration or opioid/route switching within a week (Ts). Patients were also asked about their pain intensity reported 15 days before admission (T-15). Doses of opioids and duration of opioid use were recorded. Patients were also assessed for the presence of incident pain, neuropathic pain, alcoholism, delirium, and symptom intensity, including items representing psychological distress. One week after or at time of stabilization (Ts), the opioid response was clinically graded as follows: (1) good pain control; (2) adequate pain control requiring more aggressive opioid escalation; (3) adequate pain control associated with the occurrence of adverse effects; (4) incapacity to achieve pain control within a week. Opioid escalation indexes and days for dose finding were also recorded. RESULTS: Pain intensity at T0 and at T-15, opioid doses, duration of opioid therapy, and age were associated with more complex analgesic therapies, which were effective in almost all patients within a week. CONCLUSION: High levels of pain intensity, often due to previous undertreatment, are predictive of more complex analgesic treatment. Opioid tolerance, as well as younger age, may also play a role.

The use of fentanyl buccal tablets for breakthrough pain by using doses proportional to opioid basal regimen in a home care setting.

The dose of rapid onset opioids to be given for breakthrough cancer pain (BTcP) is controversial. Dose proportional to the basal opioid regimen seem to be safe and effective in hospital units. However, data in other less protected settings, like home care, are lacking. The aim of this open-label study was to assess the efficacy and safety in a group of patients with BTcP followed at home, after giving a dose of fentanyl buccal tablets (FBT) proportional to the opioid basal regimen, skipping the steps for dose titration. Consecutive patients admitted to a home care program presenting BTcP episodes and receiving stable doses of opioids for background pain were selected. Data from four consecutive episodes of BTcP were collected. For each episode, patients were instructed to routinely collect changes in pain intensity and severe adverse effects when pain got severe (T0) and to reassess the same items 15 min after FBT, given as a rescue medication in doses proportional to the daily opioid doses used for background pain (T15). One hundred twenty episodes of BTcP were recorded in 30 patients. One hundred eight episodes were defined as successfully treated, while 12 episodes required a further administration of opioids. Pain intensity significantly decreased at T15 (p < 0.001). In 95.5 and 90.8 % of episodes treated, there was a reduction in pain intensity of more than 33 and 50 %, respectively. No relevant adverse effects were recorded, even in older patients. This study suggests that FBT given in doses proportional to the basal opioid regimen for the management of BTcP is very effective and safe in clinical practice in the home care setting.

Orphan symptoms in advanced cancer patients followed at home.

Orphan symptoms are rarely assessed, particularly at home. The aim of this multicenter prospective study was to assess the prevalence of these symptoms and eventual factors possibly associated in advanced cancer patients at admission of a home care program. A prospective study was performed at three home care programs in Italy. Patients' data were collected, including age, sex, diagnosis, and Karnofsky status. Possible contributing factors were analyzed; preexisting neurological diseases, cerebral metastases, hyperthermia, diabetes, a state of dehydration clinically evident and/or oliguria, possible biochemical parameters when available, data regarding recent chemotherapy, opioids and doses, use of neuroleptics, benzodiazepine or anticonvulsants, corticosteroids, anti-inflammatory, and antibiotics were collected. Myoclonus, hiccup, sweating, pruritus, and tenesmus, either rectal or vesical, were assessed, according to a preliminary definition, at time of home care program admission. Three hundred sixty-two patients were surveyed at the three home care programs. Globally, 48 patients presented one or more orphan symptoms in the period taken into consideration, and 7 patients presented more than 1 symptom. One patient presented occasional and diffuse myoclonus. Nineteen patients presented sweating, 13 patients presented pruritus, and 14 patients presented hiccup. Finally, nine patients presented rectal or vesical tenesmus. There was a significant correlation between sweating and transdermal fentanyl use (P = 0.044), fever (P = 0.001), hiccup (P < 0.0005), and vesical tenesmus (P = 0.028). Pruritus was not associated to any factor. Hiccup was associated with gender (males, P = 0.006) and sweating (P < 0.0005). Vesical tenesmus was associated with fever (P = 0.019) and sweating (P = 0.028). Although the symptoms examined have a low prevalence in advanced cancer patients admitted to home care, the distress for patients may be high and deserve further analyses. Given the low prevalence of these symptoms, large studies are needed to find possible associated factors.

The VES-13 and G-8 tools as predictors of toxicity associated with aromatase inhibitors in the adjuvant treatment of breast cancer in elderly patients: A single-center study.

Background: Adjuvant hormone treatment of postmenopausal breast cancer is mainly based on aromatase inhibitors. Adverse events associated with such class of drugs are particularly severe in elderly patients. Therefore, we investigated the possibility of ab initio predict which elderly patients could encounter toxicity. Methods: In light of national and international oncological guidelines recommending the use of screening tests for multidimensional geriatric assessment in elderly patients aged ≥70 years and eligible for active cancer treatment, we assessed whether the Vulnerable Elder Survey (VES)-13 and the Geriatric (G)-8 could be predictors of toxicity associated with aromatase inhibitors. Seventy-seven consecutive patients aged ≥70 diagnosed with non-metastatic hormone-responsive breast cancer and therefore eligible for adjuvant hormone therapy with aromatase inhibitors, were screened with the VES-13 and the G-8, and underwent a six-monthly clinical and instrumental follow-up in our medical oncology unit, from September 2016 to March 2019 (30 months). Said patients were identified as vulnerable (VES-13 score ≥3 or G-8 score ≤14) and fit (VES-13 score <3 or G-8 score >14). The likelihood of experiencing toxicity is greater among vulnerable patients. Results: The correlation between the VES-13 or the G-8 tools and the presence of adverse events is equal to 85.7% (p = 0.03). The VES-13 demonstrated 76.9% sensitivity, 90.2% specificity, 80.0% positive predictive value, 88.5% negative predictive value. The G-8 demonstrated 79.2% sensitivity, 88.7% specificity, 76% positive predictive value, 90.4% negative predictive value. Conclusion: The VES-13 and the G-8 tools could be valuable predictors of the onset of toxicity associated with aromatase inhibitors in the adjuvant treatment of breast cancer in elderly patients aged ≥70.

Can malignant bowel obstruction in advanced cancer patients be treated at home?

Eleven advanced cancer patients affected by malignant bowel obstruction (MBO) were treated at home with a combination of octreotide, metoclopramide, morphine, and dexamethasone. In all patients, we observed a prompt control of gastrointestinal symptoms and recovery of bowel movements within 1-5 days. Based on our results, a combination of drugs with different mechanisms of action allows an effective and safe treatment for MBO at home. Further studies with larger number of patients are warranted to confirm these preliminary data.