Sexuality in breast cancer survivors: sexual experiences, emotions, and cognitions in a group of women under hormonal therapy.

BACKGROUND: Earlier diagnosis and improved treatments have led to better outcomes in breast cancer, making quality of life a key issue. Sexuality represents a pillar of quality of life, although it is often neglected by both healthcare providers and patients when it comes to cancer. This study aims to explore the differences in sexual functioning, distress, psychopathology, emotions, and cognitions between breast cancer patients under hormonal treatment and controls. METHODS: Seventy-nine women (age range between 24 and 69 years) in hormonal therapy for breast cancer completed a self-reported protocol. A matched control group of 103 women was randomly extracted from an Italian general population database. Eight self-report questionnaires exploring biopsychosocial factors were administered. RESULTS: The current study showed an impaired sexuality in breast cancer patients compared to controls. Breast cancer women under hormonal treatment were characterized by diminished or absent sexual activity (chi2 = 36.16; p < 0.001), lower level of sexual functioning in all areas except for pain (F(1,180) = 8.1; p < 0.01), higher sexual (F(1,180) = 10.08; p < 0.001) and psychological distress (F(1,180) = 6.23; p < 0.05), higher scores in Difficulties in Identifying Feelings (F(1,180) = 7.31; p < 0.01) and Externally Oriented Thinking (F(1,180) = 6.64; p < 0.05), higher level of negative emotions related to sexuality (F(1,180) = 11.13; p < 0.001), and more rigid cognition towards peculiar aspects of sexuality, such as Failure Disengagement Thoughts (F(1,180) = 22.01; p < 0.001) and Age related Beliefs (F(1,180) = 5.7; p < 0.05). CONCLUSIONS: Health care providers do not usually assess those issues in their routine practice, so that sexuality remains an unmet need with remarkable effects on general health and quality of life.

Randomised clinical trial: faecal microbiota transplantation by colonoscopy plus vancomycin for the treatment of severe refractory Clostridium difficile infection-single versus multiple infusions.

BACKGROUND: Faecal microbiota transplantation (FMT) is a highly effective treatment against recurrent Clostridium difficile infection. Far less evidence exists on the efficacy of FMT in treating severe Clostridium difficile infection refractory to antibiotics. AIM: To compare the efficacy of two FMT-based protocols associated with vancomycin in curing subjects with severe Clostridium difficile infection refractory to antibiotics. METHODS: Subjects with severe Clostridium difficile infection refractory to antibiotics were randomly assigned to one of the two following treatment arms: (1) FMT-S, including a single faecal infusion via colonoscopy followed by a 14-day vancomycin course, (2) FMT-M, including multiple faecal infusions plus a 14-day vancomycin course. In the FMT-M group, all subjects received at least two infusions, while those with pseudomembranous colitis underwent further infusions until the disappearance of pseudomembranes. The primary outcome was the cure of refractory severe Clostridium difficile infection. RESULTS: Fifty six subjects, 28 in each treatment arm, were enrolled. Twenty one patients in the FMT-S group and 28 patients in the FMT-M group were cured (75% vs 100%, respectively, both in per protocol and intention-to-treat analyses; P = 0.01). No serious adverse events associated with any of the two treatment protocols were observed. CONCLUSIONS: A pseudomembrane-driven FMT protocol consisting of multiple faecal infusions and concomitant vancomycin was significantly more effective than a single faecal transplant followed by vancomycin in curing severe Clostridium difficile infection refractory to antibiotics. Clinical-Trials.gov registration number: NCT03427229.

FLORENCE: a randomized, double-blind, phase III pivotal study of febuxostat versus allopurinol for the prevention of tumor lysis syndrome (TLS) in patients with hematologic malignancies at intermediate to high TLS risk.

BACKGROUND: Serum uric acid (sUA) control is of key relevance in tumor lysis syndrome (TLS) prevention as it correlates with both TLS and renal event risk. We sought to determine whether febuxostat fixed dose achieves a better sUA control than allopurinol while preserving renal function in TLS prevention. PATIENTS AND METHODS: Patients with hematologic malignancies at intermediate to high TLS risk grade were randomized to receive febuxostat or allopurinol, starting 2 days before induction chemotherapy, for 7-9 days. Study treatment was blinded, whereas daily dose (low/standard/high containing allopurinol 200/300/600 mg, respectively, or fixed febuxostat 120 mg) depended on the investigator's choice. The co-primary end points, sUA area under curve (AUC sUA1-8) and serum creatinine change, were assessed from baseline to day 8 and analyzed through analysis of covariance with two-sided overall significance level of 5%. Secondary end points included treatment responder rate, laboratory and clinical TLS incidence and safety. RESULTS: A total of 346 patients (82.1% intermediate TLS risk; 82.7% assigned to standard dose) were randomized. Mean AUC sUA1-8 was 514.0 ± 225.71 versus 708.0 ± 234.42 mgxh/dl (P < 0.0001) in favor of febuxostat. Mean serum creatinine change was -0.83 ± 26.98% and -4.92 ± 16.70% for febuxostat and allopurinol, respectively (P = 0.0903). No differences among secondary efficacy end points were detected. Drug-related adverse events occurred in 6.4% of patients in both arms. CONCLUSION: In the largest adult trial carried out in TLS prevention, febuxostat achieved a significant superior sUA control with one fixed dose in comparison to allopurinol with comparable renal function preservation and safety profile. CLINICAL TRIAL REGISTRATION: NCT01724528.

Dose-finding/phase II trial: bevacizumab, immunotherapy, and chemotherapy (BIC) in metastatic renal cell cancer (mRCC). Antitumor effects and variations of circulating T regulatory cells (Treg).

The aim of this study was to explore the efficacy and toxicities of a combined regimen of bevacizumab plus immunotherapy and chemotherapy (BIC) and the circulating T regulatory cells (Treg) in metastatic renal cell cancer (mRCC). Nephrectomized mRCC patients were enrolled into a multicenter single-arm dose-finding study with five escalated dose levels of chemotherapy with intravenous gemcitabine and 5-fluorouracil associated with fixed intravenous doses of bevacizumab, subcutaneous low doses of interleukin-2, and interferon-α-2a. An expanded cohort (phase II study) was treated at the recommended dose for additional safety and efficacy information according to minimax Simon two-stage design. Blood samples for Treg were collected and evaluated by fluorescence-activated cell sorting (FACS) analysis on cycle 1. Fifty-one patients were entered to receive one of five dose levels. Median age was 58 years (male 67 %, pretreated 49 %): 15 patients were low risk according to Memorial Sloan-Kettering Cancer Center (MSKCC) criteria, while 27 and nine were respectively intermediate- and high-risk patients. More frequent grade 3 and 4 toxicities included nonfebrile neutropenia, thrombocytopenia, and fever. Among patients evaluable for response (49), 29.5 % had partial response and 37 % stable disease. Overall median time to progression and median overall survival were 8.8 and 22.67 months, respectively. We observed a rapid increase in the percentage of Treg after immunotherapy and a reduction after bevacizumab only in patient who obtained a partial response or stable disease. The BIC was feasible, well tolerated, and shown interesting activity. Further studies are needed to explore if Treg could have a role in clinical response in mRCC treated with bevacizumab.

A new freezing and storage procedure improves safety and viability of haematopoietic stem cells and neutrophil engraftment: a single institution experience.

BACKGROUND AND OBJECTIVES: Autologous peripheral blood stem cell transplantation has recently become a standard therapeutic approach to virus-related or infected haematological malignancies. Collection, manipulation, storage and thawing of leukapheresis products in this subset of patients require strict monitoring to prevent infection risk for operators and risk of contamination for other stored bags. MATERIALS AND METHODS: This is a non-randomized retrospective observational study. In the 2000-2002 period, a single bag freezing procedure was used for autologous peripheral blood stem cell transplantation. Bags were stored in tanks containing liquid and gas phase nitrogen. In 2002, the processing procedure was revised, and a second additional safety bag and a new storage tank containing jacketed liquid nitrogen have been used. RESULTS: A total of 524 bags were thawed, of which 121 processed with the single bag method and 403 with the double bag method. Forty-nine and 109 patients were infused respectively. The observed rupture rate with the single bag in liquid and gas phase nitrogen was 17 and 2.5%, respectively, against a rupture rate as little as 0.24% with the new methodology. Viability revealed levels of 84.4% +/- 6.1% and 96.9% +/- 2.4% for the single and double-bag respectively. This statistically significant (P < 0.0001) difference correlated with better neutrophil engraftment. CONCLUSIONS: The new proposed method, based on a double bag and storage freezer without liquid or gas phase nitrogen into a cryogenic chamber, significantly reduces bag rupture and bio-hazard and improves stem cell viability and neutrophil engraftment remarkably.

Plasma HHV-8 viral load in HHV-8-related lymphoproliferative disorders associated with HIV infection.

This is a mono-institutional analysis of the clinical features, immunological and virological findings, and prognostic factors of patients with HIV infection and HHV-8-lymphoproliferative disorders. Patients with Multicentric Castleman Disease and HHV-8-related lymphoma diagnosed and treated from April 1987 to June 2004 were included in the study. HHV-8 and HIV plasma viral load, CD4+ count, hematologic parameters, and general wellbeing (performance status) were assessed at the onset of the diseases and analyzed in order to identify possible prognostic factors. Nine patients with Multicentric Castleman disease, and 16 with HHV-8-related lymphomas (13 primary effusion lymphomas and 3 solid lymphomas), were diagnosed and treated out of 327 HIV-related non-Hodgkin's lymphomas. Four patients with Multicentric Castleman disease received only antiretroviral drugs; 5 HAART plus oral etoposide. Nine patients with primary effusion lymphoma were treated with a CHOP-like regimen (Cyclophosphamide, Prednisone anthracyclines, Vinca alkaloids, Bleomycin, Etoposide) and HAART; 1 with etoposide and HAART, 1 with HAART alone. The patients with solid lymphoma underwent CHOP-like chemotherapy. Patients with Multicentric Castleman disease showed lower median values of HHV-8 viral load and longer overall survival compared with HHV-8-related lymphomas. Patients with viral load of HHV-8, >40,000 cp/ml had a significant shorter overall survival. In the univariate analysis, HHV-8-related lymphoma, HHV-8 viral load >40,000 cp/ml and performance status >2 were associated with an increased risk of death. Multivariate analysis confirmed the diagnosis of lymphoma as an independent predictor of shorter survival.

Monthly ibandronate suppresses serum CTX-I within 3 days and maintains a monthly fluctuating pattern of suppression.

UNLABELLED: Bone turnover markers such as serum C-terminal cross-linking telopeptide of type I collagen (CTX-I) can be used to assess drug efficacy in osteoporosis. This study evaluated the pattern of CTX-I suppression in postmenopausal osteoporotic women receiving ibandronate. Ibandronate decreased serum CTX-I levels within 3 days of therapy initiation. Over 6 months, the levels remained suppressed below baseline. INTRODUCTION: This randomized, double-blind, placebo-controlled study evaluated the rapidity of onset and pattern of suppression of the bone resorption marker serum CTX-I in women with postmenopausal osteoporosis (PMO) who received once-monthly oral ibandronate. METHODS: Women diagnosed with PMO received once-monthly oral ibandronate (150 mg) or placebo for 6 months. Serum CTX-I was measured at baseline and after study dose administration on day 3 (month 1 only) and days 7, 14, 21, and 28 (months 1-6). Bone-specific alkaline phosphatase was measured on days 7 and 28 (months 1-6). RESULTS: This study enrolled 67 women: 49 received ibandronate, 17 received placebo, and one took no study drug. At day 3, median reduction in serum CTX-I from baseline was 70.2% with ibandronate and 6.0% with placebo (difference, -64.2%; 95% confidence interval, -80.3% to -46.2%; p < 0.0001). In women receiving ibandronate, serum CTX-I levels remained consistently below baseline, exhibiting a regular monthly fluctuating pattern of suppression over 6 months. Ibandronate was well-tolerated. CONCLUSIONS: Monthly ibandronate decreased serum CTX-I within 3 days. Over 6 months, in women receiving once-monthly ibandronate, serum CTX-I remained suppressed below baseline. A monthly fluctuation, related to time from last dose, was observed.

Recent thymic emigrants in lymphoma patients with and without human immunodeficiency virus infection candidates for autologous peripheral stem cell transplantation.

Signal joint T cell receptor excision circles (sjTRECs) have been reported as a clinical marker to measure the potential for recovery of the immune system after immunosuppressive treatments. The aim of this study was to investigate the thymic regenerative potential in 55 human immunodeficiency virus (HIV)-1 infected (HIV(+)) and non-infected (HIV(-)) lymphoma patients, candidates for autologous stem cell transplantation (ASCT). Moreover, the possible associations between sjTRECs and other immunological and clinical parameters were examined. SjTRECs levels in peripheral blood mononuclear cells (PBMCs) were quantified by real-time polymerase chain reaction and T lymphocyte subsets were analysed by flow cytometry. Our data showed that sjTRECs were reduced in lymphoma patients compared to healthy controls, although a weak significant association between low sjTRECs levels and increasing age was maintained [odds ratio (OR) = 4.00; 95% confidence interval (CI) 1.09-17.17]. We found that different chemotherapeutic treatments seem to induce similar effects on the thymic reservoir, independently from their intensity (type and number of cycles of previous chemotherapy). Results from multivariate models including adjustment for patients' sex, type of lymphoma and type of chemotherapy showed that thymic output was independent from HIV infection (OR, 0.95; 95% CI 0.20-4.48). SjTRECs levels correlated with naive T cell subsets in overall lymphoma patients and after stratification by HIV infection (r > 0.37). HIV replication should be maximally suppressed to properly evaluate thymic output by sjTREC markers. Our results suggested that de novo T cell generation is maintained partially in pretreated recurrent lymphoma patients, candidates for ASCT, and could contribute to restore the immune function after transplantation.

MUC-1 (CA 15-3 antigen) as a highly reliable predictor of response to EGFR inhibitors in patients with bronchioloalveolar carcinoma: an experience on 26 patients.

BACKGROUND: Bronchioloalveolar carcinoma (BAC) is a histological subtype of non-small cell lung cancer (NSCLC), particularly of adenocarcinoma. Given its multifocality and the poor activity of chemotherapy, there is no established treatment for BAC, although promising results have been achieved with inhibitors of the epidermal growth factor receptor (EGFR). No tumor marker has been validated in the diagnosis and follow-up of lung cancer, in particular to predict the outcome of treatment with EGFR inhibitors. PURPOSE: As CA 15-3 antigen serum levels are reported to be pathologically abnormal in adenocarcinoma of the lung, we chose this tumor marker to monitor treatment with EGFR inhibitors of patients affected by adenocarcinoma with BAC features or pure BAC. PATIENTS AND METHODS: We collected data from 26 consecutive Caucasian patients with BAC, mostly women and never smokers, who received EGFR inhibitors. RESULTS: We noticed that all patients with normal CA 15-3 serum levels at baseline (15/26, 57.7%) showed a response to EGFR inhibitors, whereas all patients with abnormal CA 15-3 serum levels (11/26, 42.3%) did not. CONCLUSION: Our data suggest that CA 15-3 levels might be a predictive factor for the response to EGFR inhibitors in patients with BAC.

Cetuximab/targeted chemotherapy in an HIV-positive patient with metastatic colorectal cancer in the HAART era: a case report.

Recent data have shown the efficacy of cetuximab/Folfiri regimen in patients with chemotherapy-resistant metastatic colorectal cancer. In the literature there are no data about this treatment in HIV-positive patients with metastatic colorectal cancer. At the Aviano Cancer Center, we used the cetuximab/Folfiri regimen and concomitant HAART in an HIV-positive patient with metastatic colorectal cancer. The patient experienced acceptable non-hematological toxicity, without any opportunistic infection and his HIV infection was kept under control. This case suggests that, in the HAART era, a multidisciplinary approach can be offered to HIV patients with advanced cancer when they have good performance status, resulting in efficacious control of the HIV infection.

Mitoxantrone, vinorelbine and prednisone (MVD) in the treatment of metastatic hormonoresistant prostate cancer--a phase II trial.

A total of 28 patients were treated with mitoxantrone, vinorelbine and prednisone every 3 weeks. In all, 11 patients (46%) had a significant prostate-specific antigen decline for a median duration of 11.4 months. Eight patients (33%) achieved a partial response on pain, while seven (29%) obtained a stabilisation of the symptom. Median duration of the response was 9.5 months. A confirmed partial response was obtained in three out of seven patients who had bidimensionally measurable disease. Toxicity was manageable. Our study provides further support to the concept of combined antimicrotubule therapy for metastatic harmonoresistant prostate cancer, promoting the exploration of new regimens containing antimicrotubule agents in addition to mitoxantrone-prednisone.

Practical issues in bone mineral density testing.

Osteoporotic fractures are a source of morbidity and mortality among postmenopausal women. Clinicians must strive to identify women at risk for osteoporotic fracture and institute proper prophylactic or treatment regimens to decrease the incidence of fractures. The advent of more sensitive, less expensive, and portable bone mineral density assessment techniques, coupled with new strategies for identifying risk factors, has made it easier for clinicians to diagnose this debilitating disease before a fracture occurs. The hope is that bone mineral density testing will result in the early identification of women at risk for osteoporosis, thereby reducing the incidence of osteoporotic fractures.

The effects of CD40 ligation on peripheral blood mononuclear cell interleukin-12 and interleukin-15 production and on monocyte CD14 surface antigen expression in human immunodeficiency virus-positive patients.

Human immunodeficiency virus (HIV) infection causes dysregulation of surface phenotype, of accessory function and of cytokine production from peripheral blood mononuclear cells (PBMCs). As CD40 ligation induces several functional activities in these cells, this stimulation may partially mimic the situation occurring in vivo during an antigen-driven immune response. The aim of this study was to measure cytokine production and immunophenotypic changes induced by CD40 stimulation of PBMCs from HIV-positive patients. Under these experimental conditions, total and heterodimeric interleukin (IL)-12 production from PBMCs was similar, while IL-10 production was increased in HIV-positive patients compared with controls. On the contrary, CD40 ligation did not induce IL-15 production by PBMCs. Surface CD14 was down-modulated, as a consequence of CD40 stimulation, on monocytes from healthy controls but not on monocytes from HIV-positive patients. These data demonstrate that some of the CD40-mediated signals are disturbed in HIV-positive patients. These disturbances may contribute to the immune dysfunction seen in HIV infection.

Dynamics of provirus load and lymphocyte subsets after interleukin 2 treatment in HIV-infected patients.

The association of antiretroviral agents plus interleukin 2 (IL-2) represents an efficient approach to the treatment of HIV+ subjects. While the effects of IL-2 on the immune system have been investigated, little is known concerning its impact on HIV dynamics. Two antiretroviral drugs control HIV viremia, but have minimal effects on the proviral load, a predictor of disease progression and response to therapy. The aim of this study was to define the effect of rIL-2 on HIV proviral copy numbers and its relationship to changes in CD4+ and CD8+ subsets. Twelve HIV+ patients with CD4 cell counts between 200 and 500 cells/mm3 were treated with six cycles of subcutaneous rIL-2, in combination with zidovudine and didanosine. This regimen resulted in a rapid and durable decrease in proviral load in the peripheral blood, in an increase in CD8+ lymphocytes, and in the emergence of a CD4+CD45RA+ T subset. These results demonstrate that the rationale for IL-2 administration to HIV+ patients may depend not only on its effects on the immune system, but also on the reduction of the number of infected cells, reinforcing the notion that IL-2 can have a favorable impact on the natural history of HIV infection.

Brain positron emission tomography (PET) in chronic fatigue syndrome: preliminary data.

Chronic fatigue syndrome (CFS) has been widely studied by neuroimaging techniques in recent years with conflicting results. In particular, using single-photon emission computed tomography (SPECT) and perfusion tracers, hypoperfusion has been found in several brain regions, although the findings vary across research centers. The objective of this study was to investigate brain metabolism of patients affected by CFS, using [18F]fluorine-deoxyglucose (18FDG) positron emission tomography (PET). We performed 18FDG PET in 18 patients who fulfilled the criteria of the working case definition of CFS. Twelve of the 18 patients were females; the mean age was 34 +/- 15 years (range, 15-68) and the median time from CFS diagnosis was 16 months (range, 9-138). Psychiatric diseases and anxiety/neurosis were excluded in all CFS patients. CFS patients were compared with a group of 6 patients affected by depression (according to DSM IV-R) and 6 age-matched healthy controls. The CFS patients were not taking any medication at the time of PET, and depressed patients were drug-free for at least 1 week before the PET examination. The PET images examined 22 cortical and subcortical areas. CFS patients showed a significant hypometabolism in right mediofrontal cortex (P = 0.010) and brainstem (P = 0.013) in comparison with the healthy controls. Moreover, comparing patients affected by CFS and depression, the latter group showed a significant and severe hypometabolism of the medial and upper frontal regions bilaterally (P = 0.037-0.001), whereas the metabolism of brain stem was normal. Brain 18FDG PET showed specific metabolism abnormalities in patients with CFS in comparison with both healthy controls and depressed patients. The most relevant result of our study is the brain stem hypometabolism which, as reported in a perfusion SPECT study, seems to be a marker for the in vivo diagnosis of CFS.