Alcohol Consumption Is a Modifiable Risk Factor for Breast Cancer: Are Women Aware of This Relationship?

AIMS: Despite alcohol consumption being a dose-dependent risk factor for breast cancer, a recent study conducted in the UK found <20% of women attending breast screening programmes were aware of this relationship and proposed proper information campaigns need to be conducted. We aimed to investigate the awareness of this relationship among a related sample of Italian women to evaluate whether similar information campaigns should also be conducted in Italy. METHODS: The questionnaire used by the UK study was translated into Italian, slightly modified for the Italian context, validated and submitted to a sample of Italian women. RESULTS: Overall 507 women were interviewed. Among them, 160 were classified as breast cancer screening attenders (SG), 44 as symptomatic breast clinic attenders (CAG) and 303 as non-screening group (NSG). Alcohol was correctly identified as a risk factor for breast cancer by 16.9, 11.4 and 14.9% of participants of SG, CAG and NSG, respectively without differences between the three groups. Despite the methodological differences, the rates of participants who correctly identified alcohol as a risk factor among women attending breast screening programmes were surprisingly similar between the study conducted in UK (15.7%) and the present study (16.9%). CONCLUSION: The results of the present study confirm the limited awareness of the relationship between alcohol consumption and risk of developing breast cancer among women and suggest the urgent need to conduct proper awareness-raising campaigns to counter this in the Italian female population.

Experiencing communication related to knowing the cancer diagnosis and prognosis: A multi-perspective interpretative phenomenological study.

PURPOSE: To understand the phenomenon of communication related to knowing the diagnosis and prognosis, by exploring the perspectives of patients with advanced cancer and those of their caregivers, physicians and nurses. METHODS: Drawing upon a multi-perspective design, a total of 27 semi-structured interviews involving four different groups of stakeholders (7 patients, 7 caregivers, 6 physicians, and 7 nurses) -who were linked by a carer-cared relationship-were conducted in two Oncology Departments of two Italian hospitals. Interpretative Phenomenological Analysis was used to interpret the participants' narratives. RESULTS: Two overarching themes were identified: The first theme "the «what is it?¼ and the «what will happen to me?¼" illustrates the two different paths of communication of diagnosis and prognosis. The second theme "Matching and mismatching in identifying the others as speakers" shows that not each of the four parties recognizes the others as reciprocal speakers on topics related to diagnosis and prognosis, although all of them display reciprocal communication interactions. CONCLUSIONS: Communication related to diagnosis and prognosis is often handled by health professionals without a comprehensive and integrated understanding of the communication approach. There is a correspondence between the nurses' perception of their extraneousness to the diagnosis and the prognosis related communication, and the descriptions and perceptions of the nurse's role reported by the other participants. Understanding how the different groups of stakeholders reciprocally interact and influence each other, can help to identify potential positive resources and detect hindrance in the implementation of an effective patient-centered approach, while avoiding silo cultures.

Ethical perspectives in communication in cancer care: An interpretative phenomenological study.

BACKGROUND: In cancer care, many clinical contexts still lack a good-quality patient-health professional communication about diagnosis and prognosis. Information transmission enables patients to make informed choices about their own healthcare. Nevertheless, disclosure is still an ethically challenging clinical problem in cancer care. High-quality care can be achieved by understanding the perspectives of others. The perspective of patients, their caregivers, physicians and nurses have seldom been simultaneously studied. OBJECTIVE: To investigate the phenomenon of diagnosis and prognosis-related communication as experienced by patients, their caregivers, and both their attending nurses and physicians, to enlighten meanings attached to communication by the four parties. METHODS: A qualitative study using interpretative phenomenological analysis was performed. PARTICIPANTS AND RESEARCH CONTEXT: Purposive sampling of six patients, six caregivers, seven nurses and five physicians was performed in two oncological hospitals in Italy. ETHICAL CONSIDERATIONS: Local Ethics Committee approved the study. It was guided by the ethical principles of voluntary enrolment, anonymity, privacy and confidentiality. RESULTS: Three main themes were identified: (a) the infinite range of possibilities in knowing and willing to know, (b) communication with the patient as a conflicting situation and (c) the bind of implicit and explicit meaning of communication. CONCLUSION: The interplay of meanings attached by patients, their caregivers, and their attending oncologist and nurse to communication about diagnosis and prognosis revealed complexities and ambiguities not yet settled. Physicians still need to solve the ethical tensions in their caring relationship with patients to really allow them 'to choose with dignity and being aware of it'. Nurses need to develop awareness about their role in diagnosis and prognosis-related communication. This cognizance is essential not just to assure consistency of communication within the multi-disciplinary team but mostly because it allows and enables the moral agent to take its own responsibilities and be accountable for them.

Preoperative assessment of cardiovascular risk in patients undergoing noncardiac surgery: the Orion study.

In patients undergoing noncardiac surgery risk indices can estimate patients' perioperative risk of major cardiovascular complications. The indexes currently in use were derived from observational studies that are now outdated with respect to the current clinical context. We undertook a prospective, observational, cohort study to derive, validate, and compare a new risk index with established risk indices. We evaluated 7335 patients (mean age 63±13 years) who underwent noncardiac surgery. Based on prospective data analysis of 4600 patients (derivation cohort) we developed an Updated Cardiac Risk Score (UCRS), and validated the risk score on 2735 patients (validation cohort). Four variables (i.e. the UCRS) were significantly associated with the risk of a major perioperative cardiovascular events: high-risk surgery, preoperative estimate glomerular filtration rate <30 ml/min/1.73 m2, age ≥75 years, and history of heart failure. Based on the UCRS we created risk classes 1,2,3 and 4 and their corresponding 30-day risk of a major cardiovascular complication was 0.8% [95% confidence interval (CI) 0.5-1.7], 2.5 (95% CI 1.6-5.6), 8.7 (95% CI 5.2-18.9) and 27.2 (95% CI 11.8-50.3), respectively. No significant differences were found between the derivation and validation cohorts. Receiver operating characteristic (ROC) curves demonstrate a high predictive performance of the new index, with greater power to discriminate between the various classes of risk than the indexes currently used. The high predictive performance and simplicity of the UCRS make it suitable for wide-scale use in preoperative cardiac risk assessment of patients undergoing noncardiac surgery.

Sense of coherence and physical health-related quality of life in Italian chronic patients: the mediating role of the mental component.

OBJECTIVE: To examine the relationship between sense of coherence (SOC) and physical health-related quality of life in patients with chronic illnesses by focusing on the mediating role of the mental component of quality of life. DESIGN: Cross-sectional survey design. SETTING: Secondary care; three departments of an Italian university hospital. METHODS: The participants (n=209) in the study were adult (≥18 years) outpatients with a chronic pathology (eg, diabetes, thyroid disorders or cancer) at any phase in the care trajectory (eg, pre-treatment, undergoing treatment, follow-up care). They agreed to participate in the study after providing their informed consent. Data were collected using a structured self-reporting questionnaire. Data analysis was carried out using SPSS, and mediation analysis was performed via PROCESS macro. RESULTS: The SOC score of the study sample was equivalent to that of the general population (mean difference=-2.50, 95% CI -4.57 to 0.00). Correlation analysis showed that SOC was mainly correlated to the mental component (MCS) (r=0.51, p<0.01) of quality of life and then to the physical component (PCS) (r=0.35, p<0.01). Mediation analysis showed that SOC was directly related to MCS (p<0.001, 95% CI 0.62 to 0.99) but not to PCS (p=0.42, 95% CI -0.27 to 0.12). In turn, MCS was directly related to PCS (p<0.001, 95% CI 0.76 to 1.01). The indirect effect of SOC on PCS through MCS was significant (0.71, p<0.001, bootstrap 95% CI 0.54 to 0.91), thus supporting the mediating role of the mental component of quality of life. CONCLUSION: The indirect effect suggests that SOC is a marker of quality of life, especially of the mental component. The findings show that SOC is a psychological process that impacts patients' mental health status, which in turn affects physical health. Better knowledge of a person's SOC and how it affects his/her quality of life may help to plan tailoring interventions to strengthen SOC and improve health-related quality of life.

Physician's Global Assessment in Psoriatic Arthritis: A Multicenter GRAPPA Study.

OBJECTIVE: Physician's global assessment (PGA) of disease activity is a major determinant of therapeutic decision making. This study assesses the reliability of the PGA, measured by means of 0-100 mm visual analog scale (VAS), and the additional use of separate VAS scales for musculoskeletal (PhysMSK) and dermatologic (PhysSk) manifestations in patients with psoriatic arthritis (PsA). METHODS: Sixteen centers from 8 countries enrolled 319 consecutive patients with PsA. PGA, PhysMSK, and PhysSk evaluation forms were administered at enrollment (W0) and after 1 week (W1). Detailed clinical data regarding musculoskeletal (MSK) manifestations, as well as dermatological assessment, were recorded. RESULTS: Comparison of W0 and W1 scores showed no significant variation (intraclass correlation coefficients were PGA 0.87, PhysMSK 0.86, PhysSk 0.78), demonstrating the reliability of the instrument. PGA scores were dependent on PhysMSK and PhysSk (p < 0.0001) with a major effect of the MSK component (B = 0.69) compared to skin (B = 0.32). PhysMSK was correlated with the number of swollen joints, tender joints, and presence of dactylitis (p < 0.0001). PhysSk scores were correlated with the extent of skin psoriasis and by face, buttocks or intergluteal, and feet involvement (p < 0.0001). Finally, physician and patient assessments were compared showing frequent mismatch and a scattered dot plot: PGA versus patient's global assessment (r = 0.36), PhysMSK versus patient MSK (r = 0.39), and PhysSk versus patient skin (r = 0.49). CONCLUSION: PGA assessed by means of VAS is a reliable tool to assess MSK and dermatological disease activity. PGA may diverge from patient self-evaluation. Because MSK and skin/nail disease activity may diverge, it is suggested that both PhysMSK and PhysSk are assessed.

Meeting psychosocial and health information needs to ensure quality of cancer care in outpatients.

PURPOSE: The purpose of this study was to investigate patients' and caregivers' health needs for a re-orientation program based on principles of health promotion in an Oncology Department from an Italian University Hospital. METHOD: A Cross-sectional design with qualitative and quantitative approaches was used. Participants included cancer patients and their caregivers. Information about disease concerns were collected using a survey form. Information about healthy lifestyle was obtained using motivational interviews. Information about perceived quality of oncology services was collected by a self-administered questionnaire. RESULTS: A total of 403 information requests were collected about patients' disease, 203 motivational interviews were carried out, and 219 questionnaires were collected. Overall, the results showed that patients and caregivers have healthy lifestyles even if meat consumption was high. Weak points were: poor physical space organization in the Service, long waiting times, and limited access to healthcare providers for patients. CONCLUSIONS: This study revealed the need for an approach based on health-promotion principles, with a particular focus on patient wellbeing and quality of life. The study increases awareness about the influence that an environment has on patient health, thus suggesting that changes in culture, attitude, and health services re-organization are crucial to meet total needs of the individual as a whole process.

Chronic pain following inguinal hernia repair: assessment of quality of life and medico-legal aspects.

The aim of our study was to evaluate the quality of life (QoL) of a group of patients who underwent tension-free inguinal hernia repair in light of the possible medicolegal implications. We conducted a retrospective study on the QoL of patients who underwent inguinal hernioplasty. One hundred and fifty patients who answered the SF-36 questionnaire were included in the study. Twenty-six (17.3%) had chronic pain, 18 (12%), sensory deficits, and 106 (70.6%) did not complain of any symptoms. There was no a significant deterioration in QoL compared to the reference population. In the group with chronic pain, 10 patients (38.4%) reported being very limited in performing "physically demanding activities"; 18 (69.2%) reported a deficit of performance in activities of daily living; 8 (30.7%) complained of a reduction of time spent at work because of emotional disorders. In one case the pain was particularly severe and required surgical treatment. The answers obtained through the questionnaire show that tension-free hernioplasty does not degrade patients'QoL. However in the group of patients with chronic pain examined one year after surgery, QoL had deteriorated so much that it affected the employment sphere and the social and relational sphere. Although there is a relatively low incidence and frequency of problems relating to chronic pain following inguinal hernioplasty, chronic pain can sometimes have serious effects on QoL and socio-economic and legal implications.

Population based study of 12 autoimmune diseases in Sardinia, Italy: prevalence and comorbidity.

BACKGROUND: The limited availability of prevalence data based on a representative sample of the general population, and the limited number of diseases considered in studies about co-morbidity are the critical factors in study of autoimmune diseases. This paper describes the prevalence of 12 autoimmune diseases in a representative sample of the general population in the South of Sardinia, Italy, and tests the hypothesis of an overall association among these diseases. METHODS: Data were obtained from 21 GPs. The sample included 25,885 people. Prevalence data were expressed with 95% Poisson C.I. The hypothesis of an overall association between autoimmune diseases was tested by evaluating the co-occurrence within individuals. RESULTS: Prevalence per 100,000 are: 552 rheumatoid arthritis, 124 ulcerative colitis, 15 Crohn's disease, 464 type 1 diabetes, 81 systemic lupus erythematosus, 124 celiac disease, 35 myasthenia gravis, 939 psoriasis/psoriatic arthritis, 35 systemic sclerosis, 224 multiple sclerosis, 31 Sjogren's syndrome, and 2,619 autoimmune thyroiditis. An overall association between autoimmune disorders was highlighted. CONCLUSIONS: The comparisons with prevalence reported in current literature do not show outlier values, except possibly for a few diseases like celiac disease and myasthenia gravis. People already affected by a first autoimmune disease have a higher probability of being affected by a second autoimmune disorder. In the present study, the sample size, together with the low overall prevalence of autoimmune diseases in the population, did not allow us to examine which diseases are most frequently associated with other autoimmune diseases. However, this paper makes available an adequate control population for future clinical studies aimed at exploring the co-morbidity of specific pairs of autoimmune diseases.

Patient global assessment in psoriatic arthritis: a multicenter GRAPPA and OMERACT study.

OBJECTIVE: During OMERACT 8, delegates selected patient global assessment (PGA) of disease as a domain to be evaluated in randomized controlled trials in psoriatic arthritis (PsA). This study assessed the reliability of the PGA, measured by means of 0-100 mm visual analog scale (VAS), and the additional utility of separate VAS scales for joints (PJA) and skin (PSA). METHODS: In total, 319 consecutive patients with PsA (186 men, 133 women, mean age 51 ± 13 yrs) were enrolled. PGA, PJA, and PSA were administered at enrolment (W0) and after 1 week (W1). Detailed clinical data, including ACR joint count, Psoriasis Area and Severity Index (PASI), and Hospital Anxiety and Depression Scale, were recorded. RESULTS: Comparison of W0 and W1 scores showed no significant variations (intraclass correlation coefficients for PGA 0.87, PJA 0.86, PSA 0.78), demonstrating the reliability of the instrument. PGA scores were not influenced by patient anxiety or depression, but were dependent on PJA and PSA (p = 0.00001). PJA was dependent on the number of swollen and tender joints (p < 0.00001). PSA scores were influenced by the extent of skin psoriasis and by hand skin involvement (p = 0.00001). Joint and skin disease were found not to correlate in terms of disease activity as evidenced by the swollen joint count compared to PASI (r = 0.11) and by the PJA compared to PSA (r = 0.38). CONCLUSION: PGA assessed by means of VAS is a reliable tool related to joint and skin disease activity. Because joint and skin disease often diverge it is suggested that in some circumstances both PJA and PSA are also assessed.

Cigarette smoking and appendectomy: effect on clinical course of diverticulosis.

AIM: To investigate the effect of appendectomy and cigarette smoking on the clinical course of diverticulosis. MATERIALS AND METHODS: A retrospective case-control study of 207 consecutive patients (45.8% male mean age 64.0 years), 150 with asymptomatic diverticulosis, and 57 with acute diverticulitis. Diagnosis of diverticulosis was defined on the basis of clinical and colonoscopic criteria, diverticulitis was defined by means of clinical, colonoscopic and computerised tomography criteria. Logistic regression function was used to define the relationship between the dependent variable (diverticulitis) and several covariates: sex, age, body mass index, smoking habit, and history of appendectomy. RESULTS: According to the final model, the risk of diverticulitis was 4.94-fold higher (95% confidence interval: 1.98-12.37) in patients with a history of appendectomy with emergency resection, compared to patients not submitted to appendectomy or with a history of elective resection (P < 0.001); and 2.79-fold higher (95% confidence interval: 1.30-5.96) in smokers than in non-smokers (P = 0.008). The effects of the two determinants were found to be independent, thus the cumulative risk of diverticulitis was 13.78-fold higher for smokers with a history of emergency surgical treatment. CONCLUSION: Smoking and emergency appendectomy are important predictive factors for the clinical course of diverticulosis.

Randomized phase III clinical trial of five different arms of treatment in 332 patients with cancer cachexia.

PURPOSE: A phase III, randomized study was carried out to establish the most effective and safest treatment to improve the primary endpoints of cancer cachexia-lean body mass (LBM), resting energy expenditure (REE), and fatigue-and relevant secondary endpoints: appetite, quality of life, grip strength, Glasgow Prognostic Score (GPS) and proinflammatory cytokines. PATIENTS AND METHODS: Three hundred thirty-two assessable patients with cancer-related anorexia/cachexia syndrome were randomly assigned to one of five treatment arms: arm 1, medroxyprogesterone (500 mg/day) or megestrol acetate (320 mg/day); arm 2, oral supplementation with eicosapentaenoic acid; arm 3, L-carnitine (4 g/day); arm 4, thalidomide (200 mg/day); and arm 5, a combination of the above. Treatment duration was 4 months. RESULTS: Analysis of variance showed a significant difference between treatment arms. A post hoc analysis showed the superiority of arm 5 over the others for all primary endpoints. An analysis of changes from baseline showed that LBM (by dual-energy X-ray absorptiometry and by L3 computed tomography) significantly increased in arm 5. REE decreased significantly and fatigue improved significantly in arm 5. Appetite increased significantly in arm 5; interleukin (IL)-6 decreased significantly in arm 5 and arm 4; GPS and Eastern Cooperative Oncology Group performance status (ECOG PS) score decreased significantly in arm 5, arm 4, and arm 3. Toxicity was quite negligible, and was comparable between arms. CONCLUSION: The most effective treatment in terms of all three primary efficacy endpoints and the secondary endpoints appetite, IL-6, GPS, and ECOG PS score was the combination regimen that included all selected agents.

Smoking trends and educational level in Italy in the age group 20-24, from 1950 to 2000.

Smoking represents an important world research issue because of its diffusion among people and its effects on health. This study analyses, according to gender and educational level, the prevalence of smoking, in order to highlight the relationship between sociocultural status and smoking. Prevalence was calculated, with reference to Italian national data in 2000, by dividing a weighted population of 38,720,629 into 10 five-year birth cohorts. Results suggest that smoking is no longer perceived as being socially acceptable behavior. The prevalence declines for both sexes and educational levels, but in low educational levels the decline is slower. The study limitations are noted.

Randomized phase III clinical trial of five different arms of treatment for patients with cancer cachexia: interim results.

OBJECTIVE: In April 2005 a phase III randomized study was started to establish which was the most effective and safest treatment of cancer-related anorexia/cachexia syndrome and oxidative stress in improving identified primary endpoints: increase of lean body mass, decrease of resting energy expenditure (REE), increase of total daily physical activity, decrease of interleukin-6 and tumor necrosis factor-alpha, and improvement of fatigue assessed by the Multidimensional Fatigue Symptom Inventory-Short Form (MFSI-SF). METHODS: All patients were given as basic treatment polyphenols plus antioxidant agents alpha-lipoic acid, carbocysteine, and vitamins A, C, and E, all orally. Patients were then randomized to one of the following five arms: 1) medroxyprogesterone acetate/megestrol acetate; 2) pharmacologic nutritional support containing eicosapentaenoic acid; 3) L-carnitine; 4) thalidomide; or 5) medroxyprogesterone acetate/megestrol acetate plus pharmacologic nutritional support plus L-carnitine plus thalidomide. Treatment duration was 4 mo. The sample comprised 475 patients. RESULTS: By January 2007, 125 patients, well balanced for all clinical characteristics, were included. No severe side effects were observed. As for efficacy, an interim analysis on 125 patients showed an improvement of at least one primary endpoint in arms 3, 4, and 5, whereas arm 2 showed a significant worsening of lean body mass, REE, and MFSI-SF. Analysis of variance comparing the change of primary endpoints between arms showed a significant improvement of REE in favor of arm 5 versus arm 2 and a significant improvement of MFSI-SF in favor of arms 1, 3, and 5 versus arm 2. A significant inferiority of arm 2 versus arms 3, 4, and 5 for the primary endpoints lean body mass, REE, and MFSI-SF was observed on the basis of t test for changes. CONCLUSION: The interim results obtained thus far seem to suggest that the most effective treatment for cancer-related anorexia/cachexia syndrome and oxidative stress should be a combination regimen. The study is still in progress and the final results should confirm these data.

Increased neuroactive steroid concentrations in women with bipolar disorder or major depressive disorder.

Changes in the plasma concentrations of neuroactive steroids have been associated with various neuropsychiatric disorders. However, the possible role of neuroactive steroids in bipolar disorder (BD) has remained unknown. We therefore determined the plasma levels of neuroactive steroids during the luteal phase of the menstrual cycle in women with BD or major depressive disorder (MDD). The plasma concentrations of 3alpha-hydroxy-5alpha-pregnan-20-one (3alpha,5alpha-THPROG), 3alpha,21-dihydroxy-5alpha-pregnan-20-one, progesterone, and cortisol were determined in 17 outpatients with BD, 14 outpatients with MDD, and 16 healthy control subjects. All patients were in a state of well-being and without relapse or recurrence for at least 3 months. Plasma concentrations of progesterone and 3alpha,5alpha-THPROG were significantly greater in patients than in controls, also being higher in BD patients than in MDD patients. Drug-free patients with BD or MDD showed similar differences in steroid concentrations relative to controls, as did drug-treated patients. Comorbidity with panic disorder, obsessive-compulsive disorder, or eating disorder had no effect on the association of mood disorders with steroid concentrations. Women with BD or MDD in a state of well-being showed higher plasma concentrations of progesterone and 3alpha,5alpha-THPROG in the luteal phase than did healthy controls. These differences did not seem to be attributable simply to drug treatment or to comorbidity with other psychiatric conditions in the patients.

Intrauterine smoke exposure: a new risk factor for bronchopulmonary dysplasia?

OBJECTIVE: To evaluate the role of intrauterine smoke exposure and other variables on the development of bronchopulmonary dysplasia (BPD) in infants with birth weight < 1500 g (VLBW). METHODS: This case-control study investigated 277 VLBW infants (141 cases, 136 controls) admitted at birth to neonatal intensive care unit and survived to discharge. A retrospective telephone interview provided detailed parental information supplementing clinical data. Logistic regression assessed the effects of birth weight < 1000 g, gestational age < 30 weeks (GA<30), respiratory distress syndrome (RDS), neonatal mechanical ventilation > 7 days (MV>7), patent ductus arteriosus (PDA), intrauterine smoke exposure > or = 3 months (ISE), and of parental history of asthma on BPD (oxygen dependency at 28 days with characteristic radiographic abnormalities) occurrence. RESULTS: Including all variables, only GA<30, RDS and MV>7 were significantly associated with BPD. ISE did not contribute significantly to this model (odds ratio [OR] 1.94; 95% confidence interval 0.88-4.26). Excluding iatrogenic variable MV>7, GA<30, RDS, PDA and ISE (OR 2.21; 95% confidence interval 1.03-4.76) were significantly associated with BPD. Analyzing GA as a continuous variable, the OR was 0.63 for each additional week. CONCLUSIONS: Prolonged mechanical ventilation, RDS and low gestational age were the major BPD determinants. Intrauterine smoke exposure seems to influence independently BPD development.

Association of serum IL-6 levels with comprehensive geriatric assessment variables in a population of elderly cancer patients.

The primary aim of this study was to find whether any association exists between serum levels of proinflammatory cytokines, mainly IL-6, and the most important comprehensive geriatric assessment (CGA) variables such as functional status, cognitive functions and nutrition in a population of elderly cancer patients. The secondary aims were to find whether any difference existed between: i) age groups, ii) performance status scores, iii) patients who had lost weight versus those who had not. Eighty-four elderly patients with advanced cancer were included in the study (stage III 15.4%, and stage IV 72.6%). Serum levels of IL-6 and CRP were significantly higher in elderly than in the other adult cancer patients. Among the CGA variables investigated, the most affected were functional status assessed by IADL, cognitive functions by MMSE and nutrition. The ECOG PS was shown to be significantly associated with all the dimensions of CGA investigated: poor PS (>/=2) corresponded to severe disabilities. As for the relationship of serum IL-6 with CGA variables, the strongest correlations were between IL-6 and functional status assessed by both Katz ADL (p=0.0003), IADL (p=0.0070) and nutrition (p=0.0013). Moreover, we observed an association, although not statistically significant, between functional disability (ADL and IADL) and high IL-6 levels in individuals with weight loss. IL-6 levels seem to be independently associated with all CGA variables investigated in the present study in a population of elderly cancer patients. Because the most important CGA variables, in particular functional status, have been observed to be strongly associated with survival, the present study, confirming our previously reported ones, suggests that IL-6 may be a reliable marker of disease outcome and supports the feasibility of using IL-6 as a sensitive outcome marker in studies based on novel approaches aiming at modifying age- and cancer-related biologic mechanisms.

Dose-intense phase II study of weekly cisplatin and epidoxorubicin plus medroxyprogesterone acetate and recombinant interleukin 2 in stage IIIB-IV non-small cell lung cancer.

The purpose of the study was to evaluate the effectiveness in terms of response rates, toxicity and survival of the combination chemotherapy regimen cisplatin and epidoxorubicin (epirubicin) including medroxyprogesterone acetate (MPA), recombinant IL-2 (rIL-2) and antioxidants in patients with advanced (stage IIIB-IV) non-small cell lung cancer (NSCLC). Thirty-three chemotherapy-naive patients with NSCLC were enrolled in the study and 30 of them were evaluable. The mean age of the patients was 61 years. Twenty (66.7%) out of 30 patients were >or=60 years, and 5 (16.7%) patients were >or=70 years. The ECOG performance status was 0 to 1 in 30 patients and 2 in 3 patients. Twenty-six patients (78.8%) had stage IIIB disease and 7 (21.2%) had stage IV; histology was mainly squamous cell carcinoma (72.7%). The treatment consisted of cisplatin 40 mg/m2/week and epirubicin 40 mg/m2/week both intravenously on day 1, rIL-2 1.8 MIU/day subcutaneously, MPA 1 g/day orally, alpha-lipoic acid 300 mg/day orally and N-acetyl cysteine 1.8 g/day orally. The treatment was administered for 6 weeks. Patients with a complete response (CR), partial response (PR) or stable disease (SD) continued the treatment, according to response re-evaluation, until 15 weeks. The present study reports the results of 6, 9, 12 and 15-week treatment. After 6 weeks, 30 patients were assessable for response: no CR was observed, a PR was achieved in 15 patients (50%; ORR 50%). After 15 weeks, 1 CR and 8 PR were observed (ORR 30.0%). The median follow-up period was 13 months. The median duration of response was 9 months. The median overall survival (OS) was 15 months. The one-year survival rate was 55.8%. The median progression-free survival (PFS) was 10 months. The toxicity was, as expected, mainly hematologic: neutropenia was the most significant symptom. The non-hematologic toxicity was quite low. Therefore, the treatment's toxicity was quite acceptable. There was no toxic death. The 30.0% ORR, the 15 month OS and the 10 month PFS obtained in this study are comparable with those observed with cisplatin plus epirubicin (ORR 39-54%) in phase II studies and in a previous phase III study (ORR 33%, OS 10.5 months). Moreover, the toxicity was acceptable and it was mainly hematologic. Serum levels of proinflammatory cytokines significantly decreased after treatment.

Quantitative evaluation of oxidative stress, chronic inflammatory indices and leptin in cancer patients: correlation with stage and performance status.

In advanced cancer patients, the oxidative stress could take place either at the onset of disease or as a function of disease progression. To test this hypothesis, the following parameters were investigated: the erythrocyte activity of the enzymes superoxide dismutase (SOD) and glutathione peroxidase (GPx), the serum activity of glutathione reductase (GR) and the serum total antioxidant status (TAS). The total antioxidant capacity of plasma LMWA was evaluated by the cyclic voltammetry methodology. We further determined the serum levels of proinflammatory cytokines (IL-6 and TNFalpha), IL-2, leptin and C-reactive protein (CRP). All of these parameters have been correlated with the most important clinical indices of patients such as Stage of disease, ECOG PS and clinical response. Eighty-two advanced stage cancer patients and 36 healthy individuals used as controls were included in the study. Our findings show that SOD activity was significantly higher in cancer patients than in controls and GPx activity was significantly lower in cancer patients than in controls. Serum values of IL-6, TNFalpha and CRP were significantly higher in patients than in controls. Serum leptin values of cancer patients were significantly lower than controls. SOD activity increased significantly from Stage II/ECOG 0-1 to Stage IV/ECOG 0-1, whereas it decreased significantly in Stage IV/ECOG 3. GPx activity decreased significantly in Stage IV/ECOG 2-3. An inverse correlation between ECOG PS and serum leptin levels was found. Serum levels of IL-2 decreased from Stage II/ECOG 0-1 to Stage IV/ECOG 2-3. A direct correlation between Stage/ECOG PS and serum levels of both IL-6 and CRP was observed. Cisplatin administration induced a significant increase of GPx after 24 hr. In conclusion, this is the first study that shows that several "biological" parameters of cancer patients such as antioxidant enzyme activity, cytokines, leptin and CRP strictly correlate with the most important clinical parameters of disease such as Stage and ECOG PS.