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Opioid therapy must be adjusted to the rhythm of a cancer patient&rsquo, s pain to ensure adequate symptom control at the end of life (EOL). However, to-date no study has explored the rhythm of breakthrough pain (BTP) episodes in terminally-ill cancer patients. This prospective longitudinal study was aimed at verifying the existence of a circadian rhythm of BTP episodes in terminally-ill cancer patients. Consecutive adult cancer patients at their EOL treated with long-acting major opioids to control background pain (Numeric Rating Scale &le, 3/10) were recruited from two Italian palliative care services. Using a personal diary, patients recorded the frequency and onset of BTP episodes and the analgesic rescue therapy taken for each episode over a 7-day period. Rhythms identified in BTP episodes were validated by Cosinor analysis. Overall, 101 patients were enrolled, nine died during the study period. A total of 665 BTP episodes were recorded (average of 7.2 episodes, mean square error 0.8) per patient, with 80.6% of episodes recorded between 8:00 a.m. and 12:00 a.m. At Cosinor analysis, a circadian rhythm of BTP episodes was observed, with a Midline Estimating Statistics of the Rhythm (MESOR) of 1.5, a double amplitude of 1.8, and an acrophase at 12:30 p.m. (p &lt, 0.001). Oral morphine was the most frequent analgesic rescue therapy employed. In terminally-ill cancer patients, BTP episodes follow a circadian rhythm, thus, tailoring the timing of opioid administration to this rhythm may prevent such episodes. This circadian rhythm of BTP episodes in terminally-ill cancer patients should be confirmed in larger samples.

Background: Cancer-related breakthrough pain (BTP) is a common and quite challenging pain syndrome, with significant impact on quality of life. To date, no widely recognized and validated tool for the diagnosis and evaluation of BTP exists. The Alberta Breakthrough Pain Assessment Tool (ABPAT) underwent a validation process during its development, but no experience of its implementation in clinical practice has been reported. Methods: ABPAT was tested in a cohort of cancer patients suffering from chronic severe cancer-related pain in order to assess its acceptability and efficacy as a tool for the characterization of BTP. Results: A total of consecutive 249 patients from seven different centres were included in a 2-month study period and all completed the questionnaire; 231 out of the 249 (92.8%) stated that questions were easily understandable and 217 out of the 249 (87.1%) stated that the tool allowed to explain extensively the BTP problem. Physician‐patient correlation tests about baseline BTP intensity and BTP relief by medication showed statistical significance at the level of p = 0.001 and p = 0.0001, respectively. Evaluation of the efficacy of BPT medication revealed a 78.2% of patients declaring a good relief from BTP, with a significant reduction of mean BTP numeric rating scale score (p = 0.0001), but only 55.9% of patients responded to be satisfied about time for onset of the relief. Conclusions: In this study, ABPAT resulted to be a well-accepted tool for BTP assessment and characterization in a relatively large cohort of cancer patients. It is effective in discovering the unmet needs of cancer patients and in exploring the outcomes of BTP treatment.

Objectives To compare the occurrence of depression, anxiety, self body image perception, sleep disturbances, and diminished quality of life in prostate cancer patients undergoing adjuvant androgen-deprivation therapy (ADT) as opposed to patients in follow-up alone. Methods and materials Hospital Anxiety and Depression Scale, Pittsburgh Sleep Quality Index, Restless Legs Syndrome Study Group essential diagnostic criteria, Body Image Scale and Functional Assessment of Cancer Therapy Prostate were administered to consecutive prostate cancer patients who underwent radical prostatectomy or radiation therapy and are presently either under adjuvant ADT or included in a follow-up program. Results Of the 103 patients enrolled, 49 (47.6%) were receiving adjuvant ADT and 54 (52.4%) were not. Compared with the controls, the patients undergoing ADT showed higher levels of depression ( P = 0.002), worse self body image perception ( P = 0.001), worse quality of life ( P = 0.0001) and worse sleep quality ( P = 0.04). ADT was significantly associated with depression at multivariate analysis after adjustment for age, stage, Gleason score, as well as demographic and social variables ( P = 0.001). Depression scores showed a strong inverse correlation with quality of life scores ( P Conclusions Adjuvant ADT is associated with depression, worse quality of life, and altered self body image in prostate cancer patients.

Objectives: To assess the prevalence of disorder Posttraumatic Stress (DPTS), anxiety and depression, quality of sleep and quality of life in cancer patients consecutively during chemotherapy compared to the general population, the prevalence of benchmarking Disorder Post Traumatic Stress (DPTS), anxiety and depression, quality of sleep and quality of life in cancer patients during adjuvant treatment versus cancer patients in treatment for metastatic disease. Methods: We surveyed consecutive patients undergoing chemotherapy treatment for neoplastic disease in accordance with the following instruments: the disorder Posttraumatic Stress was assessed by questionnaire Impact of Event Scale (IES), the levels of anxiety and depression through the Hospital Anxiety and Depression Scale (HADS); sleep quality with the help of the Pittsburgh Sleep Quality Index (PSQI), the quality of life through the Functional Assessment of Cancer Therapy - General (FACT-G). Results: We evaluated 173 patients, of whom 61 (35.3%) treated with adjuvant chemotherapy and 112 (64.7%) in chemotherapy for metastatic disease. In the overall population, the supremacy of Disorder Posttraumatic Stress was 8%, a sleep disorder 30%; anxiety to 15 - 20%, 15% from depression. The prevalence in the study population Disorder Posttraumatic Stress was higher compared to data in the literature (45.1% versus 8%), the largest of sleep disorders (62.8% versus 30%) of the anxiety higher (40% vs. 15-20%), the major depression (15% versus 31.1%). No significant differences were found with regard to the prevalence of disorder Posttraumatic Stress (P = 0.768), sleep disorders (P = 0.978), anxiety (p = 0.351), depression (P = 0.958) and quality of life (P = 0.675) in patients undergoing chemotherapy treatment for metastatic disease compared to patients treated adjuvante.Conclusões: The prevalence of psychological disorders in the study population appears significantly higher than in the general population; This finding confirms the need for psychiatric intervention consultation and liaison (liaison) in neoplastic patients undergoing chemotherapy. This need not differ between patients in the adjuvant treatment and those receiving treatment for metastatic disease, with no significant differences in the incidence of the disorders assessed between the two groups above.

Background: Breakthrough cancer pain (BTP) can place physical, psychological and economic burdens on patients and their productive life. By preventing instead of treating BTP after it occurs, the efficacy of analgesic treatment in cancer patients could be maximized. With this study, we investigated circadian variations in the occurrence of BTP events in cancer patients. Methods: The circadian variation of BTP was assessed in two different series (group 1, n = 47; group 2, n = 76) of advanced cancer patients suffering from severe chronic pain and undergoing analgesic treatment with major opioids. Results: BTP episodes showed a circadian pattern, with an acrophase occurring at 10:00 a.m. (p < 0.001) in all patients. When the two series of patients were considered separately, an acrophase was similarly observed, with 60% of BTP episodes recorded between 10:00 a.m. and 6:00 p.m. The circadian rhythm of BTP was maintained after stratifying the patients according to whether they had bone metastases or visceral metastases. BTP episodes negatively correlated with quality of life. Conclusions: BTP onset follows a circadian rhythm, with an acrophase occurring in the late morning.

Restless legs syndrome (RLS) is a common sensorimotor disorder characterized by uncomfortable and unpleasant sensations in the legs that are relieved by movement. This study evaluated the prevalence of RLS in a consecutive series of cancer patients during chemotherapy and examined the relationship between presence of RLS and quality of life, anxiety, and depressive symptoms in these patients.RLS was assessed according to the International RLS Study Group essential diagnostic criteria in two stages: a screening questionnaire first, followed by a sleep specialist-conducted structured diagnostic interview. The following questionnaires were administered: Functional Assessment of Cancer Therapy-General (FACT-G) for Quality-of-life (QoL) assessment; Hospital Anxiety and Depression Scale (HADS) to evaluate the levels of anxiety and depression; and Mini Mental Adjustment to Cancer Scale (Mini-MAC) to assess coping styles.A total of 257 patients were evaluated. Among them 56 were identified by the screening questionnaire to meet the criteria for RLS and 47 of whom were confirmed as affected by RLS after a structured interview, rendering a prevalence rate of 18.3%. RLS was significantly more frequent in women than men (23.7 vs. 11.8%; P = 0.01), and in patients receiving antineoplastic therapies for more than 3 months than their counterpart (21.8 vs. 10.8%; P = 0.03). Compared with those without RLS, patients with RLS had higher levels of anxiety (P = 0.0009) and depression (P = 0.001) and lower quality of life (P = 0.006). Sex-chemotherapy-duration-adjusted odds ratios of anxiety and physical well-being associated with RLS were 1.1 (95% CI 1.00-1.19; P = 0.04) and 0.7 (95% CI 0.43-1.01; P = 0.04), respectively.The prevalence of RLS in cancer patients undergoing chemotherapy is 18.3%, about double of that expected in the general population. The occurrence of RLS is much more frequent in female patients and with longer-term chemotherapy. Cancer patients afflicted by RLS have significantly higher levels of anxiety and depression, and poorer quality of life especially in the physical well-being dimension. Recognition and treatment of RLS in cancer patients is an important target in clinical management and may improve quality of life and overall health outcomes in these patients.

Traditionally, palliative care (PC) systems focused on the needs of advanced cancer patients. But, most patients needing PC have end-stage organ diseases. Similarly, PC models focused on the needs of patients in hospice or at home; however, in most cases PC is provided in acute hospitals. Indeed, the symptom burden that these patients experience in the last year of life frequently forces them to seek care in Emergency Department. The majority of them are admitted to the hospital and many die. This issue poses important concerns. Despite the efforts of attending healthcare professionals, inhospital patients do not receive optimal care near the end-of-life. Also, evidence is emerging that delay in identifying patients needing PC have a detrimental impact on their quality of life (QoL). Therefore, there is an urgent need to early and properly identify these patients among those hospitalized. Several trials reported the efficacy of PC in improving the QoL in these patients. Each hospital should ensure that a multidisciplinary PC team is available to support attending physicians to achieve the best QoL for both PC patients and their families. This review discusses the role and the impact of inhospital PC in patients with end-stage disease or advanced cancer.

The purpose of the study was to evaluate the influence of baseline haemoglobin level in predicting response to 5-fluorouracil (5FU)-based first-line chemotherapy in advanced colorectal cancer patients. Data from 631 patients were collected from three different institutions. Globally, overall response rate was 35.8% (226 out of 631). Factors influencing response rate were 5FU dose intensity (high: 43.1%, low: 34.0%, P = 0.03); oxaliplatin (yes: 45.8%, no: 22.9%, P0.0001), performance status (PS 0: 46.1%, 1: 28.8%, 2: 26.7%, P0.0001), and haemoglobin levels (or = 12 g dl(-1): 40.4%,12 g dl(-1): 29.2%, P = 0.004). In subgroup analysis significant differences in response rate between anaemic and nonanaemic patients were recorded in those patients treated with infusional chemotherapies (45.7 vs 25.5%, P0.0001), with high 5FU dose intensity (50.3 vs 32.7%, P = 0.005), with PS = 0 (49.8 vs 37.9%, P = 0.03), and with liver metastases (44.8 vs 33.8%, P = 0.002), whereas no difference was evident in those subjects treated with bolus schedules or according to gender. Anaemia was a strong predictor for activity of first-line 5FU-based chemotherapy especially in those groups that showed the best responses, for example high performance status, infusionally treated, higher 5FU dose and those with liver secondaries. Patients with higher haemoglobin levels recorded a greater response rate and a longer time to progression and survival than anaemic subjects. Prospective evaluation of role of correcting anaemia on response to therapy is justified by these results.

The aim of this study is to compare the quality of life and the levels of anxiety and depression in a relatively large group of subjects undergoing chemotherapy for soft tissue sarcoma and a control group of subjects undergoing chemotherapy for the most common types of cancer. 56 soft tissue sarcoma affected patients and 56 patients with common tumours, homogeneous in regards to stages of disease and sociodemographic characteristics, were enrolled in two oncological centres in Turin, Italy. Quality of life was assessed by Functional Assessment of Cancer Therapy-General and anxiety and depression by Hospital Anxiety and Depression Scale. All patients had ongoing chemotherapy. The comparison between the two groups shows no difference in either quality of life or in anxiety and depression. There are instead gender differences, since females in the group of common tumours show higher levels of anxiety in comparison to those affected by sarcomas, while males show, at a lower degree, the opposite trend. This study suggest that levels of Quality of Life, anxiety and depression are similar in rare and common tumours. The majority of patients are able to cope with the disease in an adaptive manner. However, for some patients the disease poses a threat to their physical and mental integrity; psychological support of these patients may reduce the development of significant morbidity and help patients to better manage the course of the disease and the effects of the treatment.

Candida albicans virulence is in part mediated by fibronectin (FN) interaction. We compared the adherence level to FN (using Becton Dickinson FN-coated plates) of several strains of yeast isolated from HIV-1 infected or uninfected subjects affected by candidiasis (30 strains from HIV+ subjects and 18 from HIV- subjects). More adhesive strains were found in HIV+ patients than in HIV- subjects. In particular a mean increase of 120 per cent as regards the total number of adhesive cells and 230 per cent as regards the adhesive cells producing germ tubes was detected in the former group of strains as compared to the latter ( p < 0.001 in both cases). The enhancement of FN expression induced by HIV-1 infection, as we have previously demonstrated, can increase interest in the adherence to FN of C. albicans strains isolated from AIDS-affected patients. Moreover, we also underline the important role played by HIV Nef protein in increasing the C. albicans aggressiveness. In fact a significant inhibitory effect of Nef on the phagocytosis of this yeast by macrophages has been demonstrated and the oxidative processes of these cells seem to be down-regulated by this protein.

Context Sleep disturbances are frequent in cancer patients during chemotherapy; the contributory role of restless legs syndrome (RLS) in this setting has never been assessed. Objectives This study investigated the role of RLS in causing sleep disturbances and altering the quality of life in cancer patients during chemotherapy. Methods Evaluation tools included the Pittsburgh Sleep Quality Index (PSQI), the RLS questionnaires, the Functional Assessment of Cancer Therapy-General, and the Hospital Anxiety and Depression Scale for quality of life and anxiety/depression assessment. The study population was 173 cancer patients. The questionnaires were administered during the third chemotherapy cycle. Patients positive for RLS were reassessed six months after the end of chemotherapy. Results In all, 58.8% of patients reported experiencing sleep disturbances (PSQI≥5) and 20% screened positive for RLS. Neither sleep disturbances nor RLS was associated with anemia, neurotoxic cytotoxic drugs, or benzamide treatment. A direct relationship was found between the PSQI and RLS (P=0.007); both PSQI and RLS scores were significantly associated with poor quality of life (P=0.008 and 0.01, respectively) and anxiety (P=0.0001 and 0.01, respectively). PSQI score also was associated with depression (P=0.0001). RLS persisted in four of the 25 RLS-positive patients reassessed at six months after chemotherapy. RLS recovery was associated with a significant reduction in sleep disturbances and improvement in quality of life. Conclusion RLS can be a contributory factor in sleep disturbances in cancer patients undergoing chemotherapy. Screening for RLS could aid in tailoring a potentially more efficacious treatment of such disturbances.

Background. Whether or not hypovitaminosis D can influence the prognosis of cancer patients and whether or not vitamin D (vitD) supplementation improves outcome remain controversial. Design. Studies evaluating the prognostic role of vitD and vitD receptor (VDR) in cancer patients and trials evaluating the efficacy of vitD administration on patient outcome were identified by a search of MEDLINE, EMBASE, ISI Web of Knowledge, and the Cochrane Library through June 2010. Results. Twenty-five studies were included. A negative prognostic role for low serum vitD level was observed in five cohort studies including patients with breast cancer (one study), colon cancer (two studies), prostate cancer (one study), and melanoma (one study), but not in two studies on non-small cell lung cancer and one study on breast cancer. Three of four studies showed that VDR+ tumors carry a better prognosis than VDR− tumors, whereas VDR polymorphisms were significantly associated with prognosis in five of 10 studies. A significant interaction between serum vitD level and VDR polymorphism was observed in one study. Three randomized trials involving advanced prostate cancer patients explored the prognostic role of vitD supplementation. A meta-analysis of these trials showed no effect on survival (pooled risk ratio, 1.07; 95% confidence interval, CI, 0.93–1.23), with strong heterogeneity among studies. Conclusion. Hypovitaminosis D seems to be associated with a worse prognosis in some cancers, but vitD supplementation failed to demonstrate a benefit in prostate cancer patients. The currently available evidence is insufficient to recommend vitD supplementation in cancer patients in clinical practice.

Metronomic chemotherapy is the administration of cytotoxic drugs at low doses, on a frequent or continuous schedule, with no extended interruption. This treatment approach can target tumor cells indirectly since it can affect the endothelium of the growing tumor vasculature and stimulates the anticancer immune response. Both the antiangiogenetic and the immunomodulatory roles of metronomic chemotherapy favor a tumor dormancy, a condition that may improve the patient outcome. Prospective clinical trials conducted in several malignancies have shown that metronomic chemotherapy can obtain disease stabilization or responses in tumors that had been made resistant in vivo to conventional chemotherapeutic regimens. Three prospective phase II trials have been conducted in patients with adrenocortical carcinoma (ACC). In all of them, patients heavily pretreated with conventional chemotherapy and mitotane have been enrolled. One trial tested the activity of the association of gemcitabine and fluoropyrimidines administered on a metronomic schedule. In this trial, 40% of patients attained a disease stabilization or disease response that was long lasting in some of them. In the remaining two trials, metronomic chemotherapy was administered in association with antiangiogenetic drugs, and the results were disappointing since no response or stable disease was obtained. In conclusion, metronomic chemotherapy can delay tumor progression in advanced ACC and deserves to be further tested. The concomitant administration of antiangiogenetic drugs may be detrimental. Several important questions remain to be addressed such as the optimal dose and most effective dosing interval, when to use the metronomic approach in the natural history of the disease, the choice of cytotoxic drugs, and the most efficacious way to integrate metronomic chemotherapy with standard therapy protocols.

To explore the use of CAM (Complementary/Alternative Medicine) in a population of cancer patients undergoing antineoplastic therapy, and to compare differences in sociodemographics, quality of life, and psychological features between CAM users and non-users.The study population was consecutive cancer patients undergoing antineoplastic treatment in three Piedmont cancer centers. Data were collected from anonymous questionnaires investigating CAM use or not, and what type if used, and sociodemographics, and through validated psychometric instruments to assess psychological features: Functional Assessment of Cancer Therapy-General, the Hospital Anxiety and Depression Scale, and the Mini Mental Adjustment to Cancer Scale.Of the 288 evaluable patients, 52 (18.1%) reported using one or more types of CAM; the most often cited were herbs, special diets and body-based practices, such as plantar reflexology, chiropractic application, and massage. On quality of life assessment, CAM users scored lower than CAM non-users for physical wellbeing (P = 0.006); no significant differences emerged for anxiety and depression and coping styles.CAM use is less prevalent in northern Italy than in most other European countries. CAM users were found to have a lower quality of life than CAM non-users.

Objectives : Cardiac involvement is frequently observed in HIV-infected patients, especially in those in the late stage of the disease. This study was designed to evaluate the impact of highly active antiretroviral therapy (HAART) in patients with cardiac involvement. Methods : A retrospective study of 1042 patients admitted to a Division of Infectious Diseases between 1989 and 1998. During the period 1989–1995, 544 patients were treated with nucleoside reverse transcriptase inhibitors (NRTI), whereas 498 patients were treated with HAART during the period 1996–1998. Results : Cardiac involvement, including arrhythmias, pericarditis, ischaemia, dilated cardiomyopathy, endocarditis, pulmonary hypertension, and myocarditis were observed in 282 of 544 (51.8%) patients treated with NRTI, compared with 93 of 498 (18.6%) patients with HAART ( P Conclusions : HAART has significantly decreased the incidence of cardiac involvement, especially pericarditis, arrhythmias, and dilated cardiomyopathy.

16007 Background: ADT increases fat body mass (FBM), decreases lean body mass (LBM); and decreases bone mineral density (BMD) in men with prostate carcinoma. No data are actually available regarding the relationship between treatment-related changes in body composition and patient outcome. Methods: Using dual energy x-ray absorptiometry (DEXA) we determined BMD, FBM and LBM at baseline and after 1 and 2 years in 50 consecutive patients with high risk non metastatic prostate cancer submitted to luteinizing hormone relasing hormone analogues (LHRH-A), recruited between 1997 and 2000. Results: patient median age (range) was 71 yrs (44–83). Nineteen patients had AUA stage B disease, 27 patients stage C and 4 patients stage D1. BMD (gm/cm2) at lumbar spine [mean, 95% Confidence Interval (CI)] was 0.943 (0.874–1.013) at baseline, 0.933 (0.866–1.00) after 1 year, and 0.927 (0.863–0.991) after 2 years (p

We assessed chromogranin A as a tissue biomarker in prostate needle biopsies or as a plasma biomarker, a risk factor for hormone refractory prostate cancer.A total of 211 patients with newly diagnosed prostate cancer treated with luteinizing hormone releasing hormone analogues constituted the study cohort. Univariate and multivariate Cox regression analyses were used to assess the predictive role of tissue and plasma chromogranin A expression.Chromogranin A expression in less than 30% or in 30% or more tumor cells was significantly associated with a shorter time to hormone refractory disease on univariate analysis (HR 2.0, 95% CI 1.3-3.1 and HR 6.0, 95% CI 2.7-12.9), or on multivariate analysis after adjusting for Gleason score, serum prostate specific antigen and disease stage (HR 1.7, 95% CI 1.0-2.8 and HR 3.9, 95% CI 1.7-9.0), respectively. Plasma chromogranin A measured at baseline (HR 3.0, 95% CI 1.8-5.2), and after 1 year (HR 5.8, 95% CI 3.1-10.1) and 2 years (HR 3.5, 95% CI 1.6-7.6), was predictive of hormone refractory risk confirming the tissue results. Plasma as well as tissue chromogranin A expression negatively correlated with overall survival.Chromogranin A expression in prostate cancer biopsies is an independent predictive factor of hormone refractory disease in patients with newly diagnosed prostate cancer on early androgen deprivation therapy. Plasma chromogranin A is also a reliable predictive marker and the predictive significance is maintained over time. These results deserve validation in another data set.

However, extravasation of pegylated liposomal doxorubicin is generally accompanied by a mild cutaneous reaction that is reversible in a few days. 2 Here, we describe a severe, recall cutaneous reaction to pegylated doxorubicin in a site of previous drug extravasation after the resumption of treatment. A 58-year-old woman with platinum-resistant ovarian cancer was treated at our institution with pegylated liposomal doxorubicin. She had received bilateral oophorectomy and hysterectomy for stage IIIC ovarian cancer with macroscopic residual disease in the peritoneum, the retrocrural lymph nodes, and the retroperitoneum. Use of six cycles of first-line chemotherapy with carboplatin (area under curve [AUC] 6) and paclitaxel (175 mg/m 2 ) on day 1 every 21 days gave a partial response. The disease progressed for the next 5 months, after which she received second-line chemotherapy with topotecan (1·5 mg/m 2

4681 Background: Adverse skeletal related events (SREs) are the major causes of quality of life impairment in bone metastatic prostate cancer patients. Methods: We evaluated the frequency of SREs i...

Aims and background The addition of oxaliplatin to the widely employed De Gramont schedule (FOLFOX regimen) in patients with metastatic colorectal cancer improved their outcome with a moderate toxicity pattern. The adaptation of the delivery rate of 5-fluorouracil, leucovorin and oxaliplatin to circadian rhythms (chronotherapy) resulted in a very high drug tolerability with clinical results at least comparable to those achieved with the FOLFOX regimen. However, chronomodulated infusion seemed to be more expensive, requiring dedicated electronic pumps and several disposable materials. The present study aimed to compare the direct costs of the two regimens and to determine whether chronotherapy was effectively more expensive than the FOLFOX regimen. Study design The direct costs of drug delivery devices derived from various publicly available sources and of toxicity management as extrapolated from two published studies considering comparable patient subsets were added and compared. Results Pump, central venous system and disposable materials for a single chronotherapy cycle were € 193 or € 212 according to whether the pumps were bought or rented, compared to € 58 for the FOLFOX regimen. Toxicity management costs were € 144 vs € 288 for the two schemes, respectively. Globally, a single course of chronotherapy cost € 337 or € 356, whereas a single FOLFOX cycle cost € 346. Conclusions Direct costs for a single chronotherapy cycle appeared to be comparable to a single course of the FOLFOX regimen. In fact, the major material cost of chronochemotherapy devices was balanced by a better tolerability profile. The overall improvement in quality of life with chronochemotherapy affecting indirect costs, such as reduction of work, and intangible costs is worthy of further pharmacoeconomic attention.

Summary In neuroendocrine differentiated breast cancer, the coexistence of both neuroendocrine and exocrine components may raise some uncertainty about the best clinical approach to adopt. We describe the case of a patient with neuroendocrine differentiated breast carcinoma with lung metastases, who experienced a partial response after epirubicin chemotherapy. During subsequent maintenance hormone therapy with letrozole, plasma chromogranin A was consistently elevated even though CT showed disease stabilization. The patient was scheduled for surgery and radical resection was performed. She is still alive and disease free after over 37 months. Anthracyclines are effective in the treatment of neuroendocrine differentiated breast carcinoma. Surgical resection of metastatic lesions can lead to a durable disease-free status. Serial evaluation of circulating chromogranin A is useful in the follow-up of these patients.

In a previous work we have evaluated some immunologic and haematologic parameters of HIV-1 positive subjects co-infected with HHV-8. A worsening of these values were generally described in these patients as compared with those HIV-1 positive, but negative for HHV-8. Now we have studied the influence of HHV-8 co-infection of HIV-1 positive subjects on the production of some cytokines to make clear the question of its role in the immuno-deregulation of the above-mentioned subjects. In particular we have analysed serum levels of IL-4 and IL-10, Th2 type T cells cytokines, IFN-gamma, an indirect marker of Th1 cells activation and IL-18, a cytokine produced by monocytic-macrophagic cells, which is able to induce IFN-gamma production and Th1 T lymphocytes activation. No significant differences were found as regards the IFN-gamma serum levels (92.1 +/- 24.3 pg ml(-1) in the case of HIV-1 positive/HHV-8 negative subjects and 96.0 +/- 17.4 pg ml(-1) in those HIV-1 positive/HHV-8 positive). In healthy subjects the mean level of this cytokine was 17.6 +/- 5.2 pg ml(-1) (significant difference with both the former values at p0.001). Moreover IL-4 and IL-10, which were undetectable in healthy individuals, showed the following values in HIV-1 positive/HHV-8 negative subjects: 31.9 +/- 2.7 pg ml(-1) and 119.8 +/- 85.1 pg ml(-1) respectively and in HIV-1 positive/HHV-8 positive subjects: 30.4 +/- 4.8 pg ml(-1) and 69.4 +/- 65.3 pg ml(-1) (not significant differences). In contrast IL-18 reached a mean level of 1001.2 +/- 360.5 pg ml(-1) in HIV-1 positive/HHV-8 negative subjects, but showed a significant reduction in HIV-1 positive/HHV-8 positive subjects (737.6 +/- 284.3 pg ml(-1) --p0.05) and presented very low levels in healthy individuals (21.3 +/- 30.3 pg ml(-1)). Moreover a significant correlation (-0.984 --p0.001) was noticed between IL-18 reduction in HIV-1 positive subjects co-infected with HHV-8 and the degree of positivity of HHV-8. These data suggest that HHV-8 co-infection has no influence on the switch Th1 --Th2 in HIV-1 positive subjects, but is able to reduce IL-18 production, useful for Th1 subset restoration.

Depressive disorders consistently worsen thequality of life of long-term surviving patients with cancer. These ad-verse events are a direct consequence of the diagnosis of malignantdiseaseand/ortheantineoplastictreatmentadministered.Thepoten-tiality of antineoplastic treatment to induce depression should becarefullyconsideredinthetreatmentdecisionmakingprocess,butthisissuehasbeenrelativelyneglectedbyoncologists.Daltonetal

Nef is a multifunctional gene of HIV which can increase virus replication either directly or by modulating the target cell's metabolism. Nevertheless the role of the exogenous Nef protein is not yet well understood. To investigate it, we studied the effects of the recombinant Nef protein on the expression of some antigens of lymphoid T-cells permissive to HIV-1 replication, and on their proliferation and on apoptosis induction. For this purpose, we utilised MT-4 and H9 T-cell lines. We evaluated FN (fibronectin), CD4 and CD71 expression in uninfected and acutely or chronically infected cells, both untreated and treated with Nef. Our studies showed a significant up-regulation of FN especially in uninfected cells, with a dose of 2.5 microg ml(-1); in contrast, a significant down-modulation of CD4 and CD71 both in uninfected and in acutely or chronically infected cells, was detected. The proliferation of H9 uninfected cells was significantly reduced 24 h after treatment with Nef protein in a dose-dependent manner (ranging from 0.02 to 2.5 microg ml(-1)); likewise a significant inhibition of proliferation of acutely and chronically infected cells was evident with 2.5 microg ml(-1). Moreover, we demonstrated a dose-dependent activity of Nef on inducing apoptosis in H9 uninfected cells and no effects of this protein on modulation of INF alpha and gamma production in peripheral blood mononucleated cells of health donors. Nef appeared to be able to increase the effect of apoptotic stimuli. In conclusion, our data suggest that in our experimental system, the exogenous Nef protein can inhibit cellular synthesis facilitating the metabolic pathway involved in virus replication. In addition it modulates the susceptibility to the HIV-1 infection and finally, that apoptosis induction or enhancement can facilitate the release of neoformed virions.

Androgen deprivation therapy (ADT) is administered in patients with locally advanced metastatic disease, those with high-risk localized disease, and those with biochemical failure. The goal is to induce a profound drop in plasma testosterone levels. This study confirms that serum testosterone levels have a prognostic role in patients with prostate cancer receiving ADT. Serum testosterone levels lower than the currently adopted cutoff seem to be associated with prognosis. Background: Controversy exists about whether testosterone serum levels at a cutoff point of 50 ng/dL during luteinizing hormone–releasing hormone analogue (LHRHA) treatment are related to the outcome of patients with prostate cancer. We assessed the relationship between serum testosterone levels after 6 months of LHRHA therapy and disease outcome in a consecutive series of patients with prostate cancer. Patients and Methods: Serum testosterone levels were measured prospectively in a cohort of patients given LHRHA for 6 months. End points were time to progression (TTP) and overall survival (OS). Results: The study population was 153 patients: 54 with metastatic disease and 99 with biochemical failure. In multivariate analysis, adjustment for age, baseline serum prostatic specific antigen (PSA) levels, Gleason score, and disease stage, testosterone levels 50 ng/dL failed to be associated with TTP and OS. A cutoff of 20 ng/dL was associated with a nonsignificant lower risk of progression (adjusted hazard ratio [HR] 0.58; 95% confidence interval [CI] 0.30-1.15; P .12) and a significant lower risk of death (adjusted HR, 0.19; 95% CI, 0.04-0.76; P .02). Only 25 patients attained serum testosterone levels 20 ng/dL. Using a receiver operating characteristic curve (ROC), we found that a testosterone value of 30 ng/dL offered the best overall sensitivity and specificity for prediction of death. Serum testosterone levels 30 ng/mL were associated with a significantly lower risk of death (adjusted HR, 0.45; 95% CI, 0.22-0.94; P .034. Conclusions: Serum testosterone levels lower than the currently adopted cutoff of 50 ng/dL have a prognostic role in patients with prostate cancer receiving LHRHA and are a promising surrogate parameter of LHRHA efficacy.

e19529 Background: breakthrough pain (BTP) is a transitory flare of pain that occurs on a background of well controlled baseline pain. BTP is highly prevalent among patients with cancer pain treate...

9032 Background: The Restless Legs Syndrome (RLS) is one of the commonest neurological sensorimotor disorders consisting in periodic limbs movements during the sleeping time that lead to severe insomnia and quality of life deterioration. The prevalence of RLS in normal population is 7 and 11% in males and females respectively. RLS correlated with female sex and iron deficiency. Chronic pain, sensory polineuropathy and the use of dopamine antagonist drugs can induce or exacerbate RLS. Dopamine agonists are extremely active drugs in controlling RLS. The prevalence of RLS in cancer patients is unknown. Methods: The presence of RLS, by means of the essential diagnostic criteria provided by the International RLS Study Group (Allen RP, Sleep Med; 2003), was tested in 257 consecutive cancer patients (119 males and 138 females) with different malignancies belonging to two different Medical Oncology centres. All patients were receiving chemotherapy. Functional Assessment of Cancer Therapy General (FACT-G), Hospital Anxiety and Depression Scale (HADS) and Mini Mental Adjustment to Cancer Scale (Mini-MAC) questionnaires were administered concomitantly to assess the impact of RLS on quality of life, anxiety or depression and styles of coping, respectively. Results: RLS was present in 47 patients (18.3%), 14 males (11.8%) and 33 females (23.9%); (p=0.01). RLS directly correlated with pain (p No significant financial relationships to disclose.