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1.
ESMO Open ; 9(5): 103005, 2024 May.
Article in English | MEDLINE | ID: mdl-38688192

ABSTRACT

Cutaneous squamous cell carcinoma (CSCC) accounts for ∼20%-25% of all skin tumors. Its precise incidence is often challenging to determine due to limited statistics and its incorporation with mucosal forms. While most cases have a favorable prognosis, challenges arise in patients presenting with locally advanced or metastatic forms, mainly appearing in immunocompromised patients, solid organ transplantation recipients, or those facing social difficulties. Traditionally, chemotherapy and targeted therapy were the mainstays for advanced cases, but recent approvals of immunotherapeutic agents like cemiplimab and pembrolizumab have revolutionized treatment options. These guidelines, developed by the Italian Association of Medical Oncologists (AIOM) using the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) approach, aim to guide clinicians in diagnosing, treating, and monitoring patients with CSCC, covering key aspects from primitive tumors to advanced stages, selected by a panel of experts selected by AIOM and other national scientific societies. The incorporation of these guidelines into clinical practice is expected to enhance patient care and address the evolving landscape of CSCC management.


Subject(s)
Carcinoma, Squamous Cell , Medical Oncology , Skin Neoplasms , Humans , Skin Neoplasms/therapy , Skin Neoplasms/diagnosis , Carcinoma, Squamous Cell/therapy , Carcinoma, Squamous Cell/diagnosis , Italy , Medical Oncology/standards , Practice Guidelines as Topic
2.
ESMO Open ; 8(6): 102037, 2023 Dec.
Article in English | MEDLINE | ID: mdl-37879235

ABSTRACT

Basal cell carcinoma (BCC) is the most common form of cancer, with a high impact on the public health burden and social costs. Despite the overall prognosis for patients with BCC being excellent, if lesions are allowed to progress, or in a small subset of cases harboring an intrinsically aggressive biological behavior, it can result in local spread and significant morbidity, and conventional treatments (surgery and radiotherapy) may be challenging. When a BCC is not amenable to either surgery or radiotherapy with a reasonable curative intent, or when metastatic spread occurs, systemic treatments with Hedgehog inhibitors are available. These guidelines were developed, applying the GRADE approach, on behalf of the Italian Association of Medical Oncologists (AIOM) to assist clinicians in treating patients with BCC. They contain recommendations with regard to the diagnosis, treatment and follow-up, from primitive tumors to those locally advanced or metastatic, addressing the aspects of BCC management considered as priorities by a panel of experts selected by AIOM and other national scientific societies. The use of these guidelines in everyday clinical practice should improve patient care.


Subject(s)
Carcinoma, Basal Cell , Skin Neoplasms , Humans , Skin Neoplasms/therapy , Skin Neoplasms/drug therapy , GRADE Approach , Hedgehog Proteins/therapeutic use , Carcinoma, Basal Cell/therapy , Carcinoma, Basal Cell/drug therapy , Medical Oncology , Italy/epidemiology
3.
Philos Trans R Soc Lond B Biol Sci ; 377(1863): 20210180, 2022 11 07.
Article in English | MEDLINE | ID: mdl-36126672

ABSTRACT

According to an evolutionist approach, laughter is a multifaceted behaviour affecting social, emotional, motor and speech functions. Albeit previous studies have suggested that high-frequency electrical stimulation (HF-ES) of the pregenual anterior cingulate cortex (pACC) may induce bursts of laughter-suggesting a crucial contribution of this region to the cortical control of this behaviour-the complex nature of laughter implies that outward connections from the pACC may reach and affect a complex network of frontal and limbic regions. Here, we studied the effective connectivity of the pACC by analysing the cortico-cortical evoked potentials elicited by single-pulse electrical stimulation of pACC sites whose HF-ES elicited laughter in 12 patients. Once these regions were identified, we studied their clinical response to HF-ES, to reveal the specific functional target of pACC representation of laughter. Results reveal that the neural representation of laughter in the pACC interacts with several frontal and limbic regions, including cingulate, orbitofrontal, medial prefrontal and anterior insular regions-involved in interoception, emotion, social reward and motor behaviour. These results offer neuroscientific support to the evolutionist approach to laughter, providing a possible mechanistic explanation of the interplay between this behaviour and emotion regulation, speech production and social interactions. This article is part of the theme issue 'Cracking the laugh code: laughter through the lens of biology, psychology and neuroscience'.


Subject(s)
Gyrus Cinguli , Laughter , Electric Stimulation/methods , Emotions/physiology , Evoked Potentials , Gyrus Cinguli/physiology , Humans , Laughter/physiology , Laughter/psychology
4.
Brain Stimul ; 15(3): 664-675, 2022.
Article in English | MEDLINE | ID: mdl-35421585

ABSTRACT

BACKGROUND: Cortico-cortical evoked potentials (CCEPs) recorded by stereo-electroencephalography (SEEG) are a valuable tool to investigate brain reactivity and effective connectivity. However, invasive recordings are spatially sparse since they depend on clinical needs. This sparsity hampers systematic comparisons across-subjects, the detection of the whole-brain effects of intracortical stimulation, as well as their relationships to the EEG responses evoked by non-invasive stimuli. OBJECTIVE: To demonstrate that CCEPs recorded by high-density electroencephalography (hd-EEG) provide additional information with respect SEEG alone and to provide an open, curated dataset to allow for further exploration of their potential. METHODS: The dataset encompasses SEEG and hd-EEG recordings simultaneously acquired during Single Pulse Electrical Stimulation (SPES) in drug-resistant epileptic patients (N = 36) in whom stimulations were delivered with different physical, geometrical, and topological parameters. Differences in CCEPs were assessed by amplitude, latency, and spectral measures. RESULTS: While invasively and non-invasively recorded CCEPs were generally correlated, differences in pulse duration, angle and stimulated cortical area were better captured by hd-EEG. Further, intracranial stimulation evoked site-specific hd-EEG responses that reproduced the spectral features of EEG responses to transcranial magnetic stimulation (TMS). Notably, SPES, albeit unperceived by subjects, elicited scalp responses that were up to one order of magnitude larger than the responses typically evoked by sensory stimulation in awake humans. CONCLUSIONS: CCEPs can be simultaneously recorded with SEEG and hd-EEG and the latter provides a reliable descriptor of the effects of SPES as well as a common reference to compare the whole-brain effects of intracortical stimulation to those of non-invasive transcranial or sensory stimulations in humans.


Subject(s)
Epilepsy , Scalp , Brain Mapping/methods , Electric Stimulation/methods , Electroencephalography/methods , Epilepsy/diagnosis , Evoked Potentials/physiology , Humans , Transcranial Magnetic Stimulation/methods
5.
ESMO Open ; 6(2): 100064, 2021 04.
Article in English | MEDLINE | ID: mdl-33711672

ABSTRACT

BACKGROUND: Checkpoint inhibitors in melanoma can lead to self-immune side-effects such as vitiligo-like depigmentation (VLD). Beyond the reported association with favorable prognosis, there are limited data regarding VLD patient features and their echo on the therapeutic outcomes. METHODS: To assess the association between VLD and a series of clinical and biological features as well as therapeutic outcomes, we built an observational cohort study by recruiting patients who developed VLD during checkpoint inhibitors. RESULTS: A total of 148 patients from 15 centers (101 men, median age 66 years, BRAF mutated 23%, M1c 42%, Eastern Cooperative Oncology Group (ECOG) status 0/1 99%, normal lactate dehydrogenase 74%) were enrolled. VLD was induced by ipilimumab, programmed cell death-1 (PD-1) inhibitors, and their combination in 32%, 56%, and 12%, respectively. The median onset was 26 weeks and it was associated with other skin and nonskin toxicities in 27% and 28%, respectively. After 3 years of VLD onset, 52% (95% confidence interval 39% to 63%) were progression free and 82% (95% confidence interval 70% to 89%) were still alive. The overall response rate was 73% with 26% complete response. Univariable analysis indicated that BRAF V600 mutation was associated with a better overall survival (P = 0.028), while in multivariable analysis a longer progression-free survival was associated with BRAF V600 (P = 0.093), female sex (P = 0.008), and M stage other than 1a (P = 0.024). When VLD occurred, there was a significant decrease of white blood cell (WBC) count (P = 0.05) and derived WBC-to-lymphocytes ratio (dWLR; P = 0.003). A lower monocyte count (P = 0.02) and dWLR (P = 0.01) were also reported in responder patients. CONCLUSIONS: Among VLD population, some features might help to identify patients with an effective response to immunotherapy, allowing clinicians to make more appropriate choices in terms of therapeutic options and duration.


Subject(s)
Immune Checkpoint Inhibitors/adverse effects , Ipilimumab/adverse effects , Melanoma , Vitiligo , Aged , Female , Humans , Immune Checkpoint Inhibitors/therapeutic use , Ipilimumab/therapeutic use , Italy/epidemiology , Male , Melanoma/drug therapy , Vitiligo/chemically induced , Vitiligo/diagnosis
6.
Cytokine Growth Factor Rev ; 51: 1-9, 2020 02.
Article in English | MEDLINE | ID: mdl-31862236

ABSTRACT

The Ninth Annual Conference of "Anticancer Innovative Therapy", organized by Fondazione IRCCS Istituto Nazionale dei Tumori di Milano (Fondazione IRCCS INT) and hosted by Hotel Michelangelo, was held in Milan on 25 January 2019. Cutting-edge science was presented in two main scientific sessions: i) pre-clinical evidences and new targets, and ii) clinical translation. The Keynote lecture entitled "Cancer stem cells (CSCs): metabolic strategies for their identification and eradication" presented by M. Lisanti, was one of the highlights of the conference. One key concept of the meeting was how the continuous advances in our knowledge about molecular mechanisms in various fields of research (cancer metabolism reprogramming, epigenetic regulation, transformation/invasiveness, and immunology, among others) are driving cancer research towards more effective personalized antineoplastic strategies. Specifically, recent preclinical data on the following topics were discussed: 1. Polycomb group proteins in cancer; 2. A d16HER2 splice variant is a flag of HER2 addiction across HER2-positive cancers; 3. Studying chromatin as a nexus between translational and basic research; 4. Metabolomic analysis in cancer patients; 5. CDK4-6 cyclin inhibitors: clinical activity and future perspectives as immunotherapy adjuvant; and 6. Cancer stem cells (CSCs): metabolic strategies for their identification and eradication. In terms of clinical translation, several novel approaches were presented: 1. Developing CAR-T cell therapies: an update of preclinical and clinical development at University of North Carolina; 2. Vγ9Vδ2 T-cell activation and immune suppression in multiple myeloma; 3. Predictive biomarkers for real-world immunotherapy: the cancer immunogram model in the clinical arena; and 4. Mechanisms of resistance to immune checkpoint blockade in solid tumors. Overall, the pre-clinical and clinical findings presented could pave the way to identify novel actionable therapeutic targets to significantly enhance the care of persons with cancer.


Subject(s)
Antineoplastic Agents/therapeutic use , Immunotherapy , Neoplasms/therapy , Therapies, Investigational , Animals , Biomarkers, Tumor , Congresses as Topic , Epigenesis, Genetic , Humans , Italy , Mice , Mutation , Neoplastic Stem Cells
7.
Cytokine Growth Factor Rev ; 44: 1-10, 2018 12.
Article in English | MEDLINE | ID: mdl-30393044

ABSTRACT

The eighth annual conference of "Innovative therapy, monoclonal antibodies, and beyond" was held in Milan on Jan. 26, 2018, and hosted by Fondazione IRCCS-Istituto Nazionale dei Tumori (Fondazione IRCCS INT). The conference was divided into two main scientific sessions, of i) pre-clinical assays and novel biotargets, and ii) clinical translation, as well as a third session of presentations from young investigators, which focused on recent achievements within Fondazione IRCCS INT on immunotherapy and targeted therapies. Presentations in the first session addressed the issue of cancer immunotherapy activity with respect to tumor heterogeneity, with key topics addressing: 1) tumor heterogeneity and targeted therapy, with the definition of the evolutionary Index as an indicator of tumor heterogeneity in both space and time; 2) the analysis of cancer evolution, with the introduction of the TRACERx Consortium-a multi-million pound UK research project focused on non-small cell lung cancer (NSCLC); 3) the use of anti-estrogen agents to boost immune recognition of breast cancer cells; and 4) the high degree of functional plasticity within the NK cell repertoire, including the expansion of adaptive NK cells following viral challenges. The second session addressed: 1) the effectiveness of radiotherapy to enhance the proportion of patients responsive to immune-checkpoint blockers (ICBs); 2) the use of MDSC scores in selecting melanoma patients with high probability to be responsive to ICBs; and 3) the relevance of the gut microbiome as a predictive factor, and the potential of its perturbation in increasing the immune response rate to ICBs. Overall, a picture emerged of tumor heterogeneity as the main limitation that impairs the effectiveness of anti-cancer therapies. Thus, the choice of a specific therapy based on reproducible and selective predictive biomarkers is an urgent unmet clinical need that should be addressed in order to increase the proportion of long-term responding patients and to improve the sustainability of novel drugs.


Subject(s)
Antibodies, Monoclonal/therapeutic use , Immunotherapy , Neoplasms/therapy , Animals , Gastrointestinal Microbiome , Humans , Neoplasms/immunology , Neoplasms/microbiology
9.
Cytokine Growth Factor Rev ; 38: 1-9, 2017 Dec.
Article in English | MEDLINE | ID: mdl-29029813

ABSTRACT

The seventh Edition of "Innovative Therapy, Monoclonal Antibodies and Beyond" Meeting took place in Milan, Italy, on January 27, 2017. The two sessions of the meeting were focused on: 1) Preclinical assays and novel biotargets; and 2) monoclonal antibodies, cell therapies and targeted molecules. Between these two sessions, a lecture entitled "HLA-antigens modulation and response to immune checkpoint inhibitor immunotherapy" was also presented. Despite the impressive successes in cancer immunotherapy in recent years, the response to immune based interventions occurs only in a minority of patients (∼20%). Several basic and translational mechanisms of resistance to immune checkpoint blockers (ICBs) were discussed during the meeting: 1. the impact of tumor microenvironment on the activity of immune system; 2. strategies to inhibit the cross-talk between extracellular matrix and myeloid-derived suppressor cells (MDSC) in the preclinical setting; 3. microRNA expression as a biomarker and as a target of therapy in non-small cell lung cancer (NSCLC); 4. the significance of complement activation pathways in response to immune checkpoint inhibitors; 5. the immunosuppressive activity of the microbiota by inducing IL-17 producing cells; and 6. modulation of HLA antigens as possible markers of response to ICB therapy. In order to overcome the deficiency in active anti-tumor T cells, several clinically applicable combination strategies were also discussed: 1. strategies to enhance the anticancer effects of immunogenic cell death inducing-chemotherapy; 2. the use of CAR T-cells in solid tumors; 3. the use of combination strategies involving oncolytic viruses and ICBs; 4. combinations of new ICBs with anti-PD-1/CTLA-4 therapy; and 4. combinations of targeted therapies and ICBs in melanoma. Overall, this conference emphasized the many novel strategies that are being investigated to improve the overall patient response to cancer immunotherapy. Optimization of biomarkers to accurately select patients who will respond to immunotherapy, coupled with combination strategies to improve long term patient survival remain critical challenges in the immuno-oncology field.


Subject(s)
Antibodies, Monoclonal/therapeutic use , Immunotherapy , Neoplasms/therapy , Animals , Humans , Neoplasms/drug therapy
10.
Eur J Clin Microbiol Infect Dis ; 36(10): 1777-1786, 2017 Oct.
Article in English | MEDLINE | ID: mdl-28501926

ABSTRACT

An outbreak of Clostridium difficile infection (CDI) caused by ribotype 027 (B1/NAP1) began in our hospital in November 2014, and produced 141 episodes in the following months. The aim of this study is to describe this outbreak, assess risk factors for recurrence of CDI-027 and to analyze the implementation of a novel treatment strategy. This is a prospective study of all patients with CDI-027, from November 2014 to November 2015. The epidemiological data were collected daily for each patient. We compared clinical characteristics and treatment between patients with and without recurrence of CDI-027. Interestingly, liver cirrhosis was present in 22% of the patients, and most of them received prophylaxis for hepatic encephalopathy with rifaximin. Patients were also taking antimicrobial drugs (93.6%) and proton pump inhibitors (80.1%). Overall, 27 (23.5%) patients had a first recurrence of CDI-027. Liver cirrhosis increased the risk of recurrence (44.4% vs 14.8%). Patients treated with a prolonged oral vancomycin regimen vs the conventional regimen (oral metronidazole or 10 days of vancomycin) had fewer recurrences (8.6 versus 44.7% [p ≤ 0.01]; OR, 0.91; 95% CI, 0.028-0.294) and less attributable mortality (0% versus 7.1%; p = 0.058). We report an outbreak of CDI-027, mainly in patients with liver cirrhosis. Recurrence of CDI-027 was more common in those patients. A novel approach involving high-dose prolonged vancomycin taper as a first-line treatment, together with a bundle of outbreak measures, seemed to reduce the number of cases of CDI-027, recurrences, and attributable mortality. Nevertheless, this approach warrants further investigation.


Subject(s)
Anti-Bacterial Agents/therapeutic use , Clostridioides difficile/classification , Clostridioides difficile/genetics , Clostridium Infections/drug therapy , Clostridium Infections/epidemiology , Disease Outbreaks , Ribotyping , Administration, Oral , Aged , Aged, 80 and over , Clostridioides difficile/isolation & purification , Clostridium Infections/microbiology , Female , Humans , Male , Metronidazole/therapeutic use , Middle Aged , Polymerase Chain Reaction , Prospective Studies , Recurrence , Risk Factors , Spain/epidemiology , Survival Analysis , Treatment Outcome , Vancomycin/therapeutic use , Young Adult
11.
Cancer Treat Rev ; 50: 1-8, 2016 Nov.
Article in English | MEDLINE | ID: mdl-27566962

ABSTRACT

Brain metastases are a common occurrence in patients with melanoma. Prognosis is poor. Radiotherapy is the main local treatment for brain metastases. Recently, immunotherapy (i.e. immune checkpoints inhibitors) showed a significant impact on the prognosis of patients with metastatic melanoma, also in the setting of patients with brain metastases. Despite various possible treatments, survival of patients with melanoma brain metastases is still unsatisfactory; new treatment modalities or combination of therapies need to be explored. Being immunotherapy and radiotherapy alone both efficient in the treatment of melanoma brain metastases, the combination of these two therapies seems logical. Moreover radiotherapy can improve the efficacy of immunotherapy and the immune system plays a relevant role in the action of radiotherapy. Preclinical data support this combination. Clinical data are more contradictory. In this review, we will discuss available therapies for melanoma brain metastases, focusing on the preclinical and clinical available data supporting the possible synergism between radiotherapy and immunotherapy.


Subject(s)
Antibodies, Monoclonal/therapeutic use , Antineoplastic Agents/therapeutic use , Brain Neoplasms/therapy , Chemoradiotherapy , Melanoma/therapy , Radiosurgery/methods , Skin Neoplasms/therapy , Brain Neoplasms/secondary , Humans , Immunotherapy , Ipilimumab , Melanoma/secondary , Nivolumab , Prognosis , Skin Neoplasms/pathology
12.
Ann Oncol ; 27(4): 732-8, 2016 Apr.
Article in English | MEDLINE | ID: mdl-26802161

ABSTRACT

BACKGROUND: Clinical responses to ipilimumab are variable in terms of onset, magnitude and duration. Upfront identification of patients who are more likely or unlikely to benefit from treatment is a major need. PATIENTS AND METHODS: Prospectively collected data from 720 advanced melanoma patients treated with ipilimumab 3 mg/kg within the Italian expanded access program were analyzed. The derived neutrophil-to-lymphocyte ratio (dNLR) was calculated from baseline peripheral blood cell counts, and receiver operating characteristic curve was used to evaluate the best cutoff for this marker. Patients were stratified according to dichotomized baseline absolute neutrophil counts (ANC), dNLR and their combination. The prognostic values of ANC and dNLR for survival were assessed using multivariate Cox proportional hazard models. A subgroup analysis including LDH in the models was also carried out. RESULTS: The median follow-up was 16.5 months. The optimal cutoff for dNLR was 3. Baseline ANC and dNLR were significantly associated with the outcome of ipilimumab-treated melanoma patients, in terms of disease progression and death (P < 0.0001 for all). Furthermore, for each elevated variable, prognosis worsened. Patients with both ANC ≥ 7500 and dNLR ≥ 3 had a significantly and independently increased risk of death [hazard ratio(HR) = 5.76; 95% confidence interval (CI) 4.29-7.75] and of progression (HR = 4.10; 95% CI 3.08-5.46) compared with patients with both lower ANC and dNLR. Patients with one of the two factors elevated displayed an intermediate risk of progression and death. The 1- and 2-year survival rates were 2% and 0%, respectively, for patients with ANC ≥ 7500 and dNLR ≥ 3, and 43% and 24%, respectively, for patients with both lower ANC and dNLR. CONCLUSIONS: Although these findings need to be confirmed and validated, we suggest that a neutrophil-based index may help risk-group stratification and assist disease-management strategies. Furthermore, the potential predictive value of this index for response to ipilimumab should be investigated in randomized clinical trials.


Subject(s)
Antibodies, Monoclonal/administration & dosage , Biomarkers, Tumor/blood , Melanoma/blood , Melanoma/drug therapy , Adolescent , Adult , Aged , Aged, 80 and over , Antibodies, Monoclonal/adverse effects , Disease-Free Survival , Female , Humans , Ipilimumab , Italy , Lymphocyte Count , Lymphocytes/pathology , Male , Melanoma/pathology , Middle Aged , Neutrophils/pathology , Prognosis
13.
Ann Oncol ; 26(11): 2267-74, 2015 Nov.
Article in English | MEDLINE | ID: mdl-26410620

ABSTRACT

BACKGROUND: The efficacy and safety of nab-paclitaxel versus dacarbazine in patients with metastatic melanoma was evaluated in a phase III randomized, controlled trial. PATIENTS AND METHODS: Chemotherapy-naïve patients with stage IV melanoma received nab-paclitaxel 150 mg/m(2) on days 1, 8, and 15 every 4 weeks or dacarbazine 1000 mg/m(2) every 3 weeks. The primary end point was progression-free survival (PFS) by independent radiologic review; the secondary end point was overall survival (OS). RESULTS: A total of 529 patients were randomized to nab-paclitaxel (n = 264) or dacarbazine (n = 265). Baseline characteristics were well balanced. The majority of patients were men (66%), had an Eastern Cooperative Oncology Group status of 0 (71%), and had M1c stage disease (65%). The median PFS (primary end point) was 4.8 months with nab-paclitaxel and 2.5 months with dacarbazine [hazard ratio (HR), 0.792; 95.1% confidence interval (CI) 0.631-0.992; P = 0.044]. The median OS was 12.6 months with nab-paclitaxel and 10.5 months with dacarbazine (HR, 0.897; 95.1% CI 0.738-1.089; P = 0.271). Independently assessed overall response rate was 15% versus 11% (P = 0.239), and disease control rate (DCR) was 39% versus 27% (P = 0.004) for nab-paclitaxel versus dacarbazine, respectively. The most common grade ≥3 treatment-related adverse events were neuropathy (nab-paclitaxel, 25% versus dacarbazine, 0%; P < 0.001), and neutropenia (nab-paclitaxel, 20% versus dacarbazine, 10%; P = 0.004). There was no correlation between secreted protein acidic and rich in cysteine (SPARC) status and PFS in either treatment arm. CONCLUSIONS: nab-Paclitaxel significantly improved PFS and DCR compared with dacarbazine, with a manageable safety profile.


Subject(s)
Albumins/therapeutic use , Dacarbazine/therapeutic use , Melanoma/diagnosis , Melanoma/drug therapy , Paclitaxel/therapeutic use , Skin Neoplasms/diagnosis , Skin Neoplasms/drug therapy , Adult , Aged , Aged, 80 and over , Antineoplastic Agents, Alkylating/therapeutic use , Disease-Free Survival , Female , Humans , Male , Middle Aged , Young Adult
15.
Eur J Clin Microbiol Infect Dis ; 34(6): 1081-5, 2015 Jun.
Article in English | MEDLINE | ID: mdl-25620782

ABSTRACT

Rapid antigen detection tests (RADTs) are immunoassays that produce results in 15 min or less, have low sensitivity (50 %), but high specificity (95 %). We studied the clinical impact and laboratory savings of a diagnostic algorithm for influenza infection using RADTs as a first-step technique during the influenza season. From January 15th to March 31st 2014, we performed a diagnostic algorithm for influenza infection consisting of an RADT for all respiratory samples received in the laboratory. We studied all the patients with positive results for influenza infection, dividing them into two groups: Group A with a negative RADT but positive reference tests [reverse transcription polymerase chain reaction (RT-PCR) and/or culture] and Group B with an initial positive RADT. During the study period, we had a total of 1,156 patients with suspicion of influenza infection. Of them, 217 (19 %) had a positive result for influenza: 132 (11 %) had an initial negative RADT (Group A) and 85 (7 %) had a positive RADT (Group B). When comparing patients in Group A and Group B, we found significant differences, as follows: prescribed oseltamivir (67 % vs. 82 %; p = 0.02), initiation of oseltamivir before 24 h (89 % vs. 97 %; p = 0.03), antibiotics prescribed (89 % vs. 67 %; p = <0.01), intensive care unit (ICU) admissions after diagnosis (23 % vs. 14 %; p = 0.05), and need for supplementary oxygen (61 % vs. 47 %; p = 0.01). An influenza algorithm including RADTs as the first step improves the time of administration of proper antiviral therapy, reduces the use of antibiotics and ICU admissions, and decreases hospital costs.


Subject(s)
Algorithms , Diagnostic Tests, Routine/methods , Influenza, Human/diagnosis , Mass Screening/methods , Adult , Antiviral Agents/therapeutic use , Child , Child, Preschool , Cohort Studies , Diagnostic Tests, Routine/economics , Female , Hospital Costs , Humans , Influenza, Human/drug therapy , Male , Mass Screening/economics , Middle Aged
16.
Ann Oncol ; 26(4): 798-803, 2015 Apr.
Article in English | MEDLINE | ID: mdl-25538176

ABSTRACT

BACKGROUND: In the NIBIT-M1 study, we reported a promising activity of ipilimumab combined with fotemustine in metastatic melanoma (MM) patients with or without brain metastases. To corroborate these initial findings, we now investigated the long-term efficacy of this combination. PATIENTS AND METHODS: This analysis captured the 3-year outcome of MM patients who received ipilimumab combined with fotemustine as first- or second-line treatment. Median overall survival (OS), 3-year survival rates, immune-related (ir) progression-free survival (irPFS), brain PFS, and ir duration of response (irDOR) for the entire population and for patients with brain metastases were assessed. Clinical results were correlated with circulating CD3(+)CD4(+)ICOS(+)CD45RO(+) or CD45RA(+) T cells, neutrophil/lymphocyte (N/L) ratios, and tumorBRAF-V600 mutational status. RESULTS: Eighty-six MM patients, including 20 with asymptomatic brain metastases that had been pre-treated with radiotherapy in 7 subjects, were enrolled in the study. With a median follow-up of 39.9 months, median OS and 3-year survival rates were 12.9 months [95% confidence interval (CI) 7.1-18.7 months] and 28.5% for the whole study population, and 12.7 months (95% CI 2.7-22.7 months) and 27.8% for patients with brain metastases, respectively. Long-term ir adverse events consisting of G1 rush and pruritus occurred in 21% of patients. The absolute increase from baseline to week 12 in 'memory' but not in 'naïve' T cells identified patients with a better survival (P = 0.002). The N/L ratio correlated with a significantly better survival at early time points. BRAF status did not correlate with clinical outcome. CONCLUSIONS: Long-term analysis of the NIBIT-M1 trial continues to demonstrate efficacy of ipilimumab combined with fotemustine in MM patients. Fotemustine does not seem to impair the immunologic activity of ipilimumab. EUDRACT NUMBER: 2010-019356-50. CINICALTRIALSGOV: NCT01654692.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Biological Therapy/mortality , Brain Neoplasms/drug therapy , Melanoma/drug therapy , Skin Neoplasms/drug therapy , Adult , Aged , Antibodies, Monoclonal/administration & dosage , Brain Neoplasms/mortality , Brain Neoplasms/secondary , Female , Follow-Up Studies , Humans , Ipilimumab , Male , Melanoma/mortality , Melanoma/pathology , Middle Aged , Neoplasm Staging , Nitrosourea Compounds/administration & dosage , Organophosphorus Compounds/administration & dosage , Prognosis , Skin Neoplasms/mortality , Skin Neoplasms/pathology , Survival Rate
17.
Pathologica ; 106(2): 41-4, 2014 Jun.
Article in English | MEDLINE | ID: mdl-25291865

ABSTRACT

INTRODUCTION: Nipple adenoma (NA) is a benign epithelial lesion of the breast that can clinically simulate Paget's disease or invasive ductal carcinoma. Therefore, correct pre-operative diagnosis is important for appropriate management. METHODS: Cytological samples may be obtained by different methods such as fine needle aspiration, nipple discharge or nipple scraping. Herein, the cytological features of three cases of NA are described in which samples were derived from nipple scraping. RESULTS: In all three cases, patients were adult females presenting with a sub-areolar nodule, showing skin ulceration in 2 of 3 cases. The nipple scraping cytological smears were characterised by a bloody background with epithelial cells arranged in clusters or singularly, showing an irregular nuclei profile. These features could simulate a malignant process. However, at higher magnification, fine nuclear chromatin with inconspicuous nucleoli and presence of myoepithelial cells were helpful to exclude malignancy. DISCUSSION: NA may present "worrisome" cytological features on smears derived from nipple scraping. Therefore, knowledge of the cytological spectrum of this lesion is important to avoid misdiagnosis.


Subject(s)
Adenoma/pathology , Breast Neoplasms/pathology , Nipples/pathology , Specimen Handling/methods , Adult , Aged , Aged, 80 and over , Diagnosis, Differential , Female , Humans , Predictive Value of Tests , Prognosis
18.
Br J Cancer ; 110(7): 1721-6, 2014 Apr 02.
Article in English | MEDLINE | ID: mdl-24619072

ABSTRACT

BACKGROUND: Retreatment with ipilimumab has been shown to re-establish disease control in some patients with disease progression. Here, we report the efficacy and safety of retreatment with ipilimumab 3 mg kg(-1) among patients participating in an expanded access programme in Italy. METHODS: Patients who achieved disease control during induction therapy were retreated with ipilimumab upon progression (3 mg kg(-1) every 3 weeks for up to four doses), providing they had not experienced toxicity that precluded further dosing. Tumour assessments were conducted after retreatment, and patients were monitored throughout for adverse events. RESULTS: Of 855 patients treated with ipilimumab, 51 were retreated upon disease progression. Of these, 28 (55%) regained disease control upon retreatment and 42% were alive 2 years after the first induction dose of ipilimumab; median overall survival was 21 months. Eleven patients (22%) had a treatment-related adverse event of any grade during retreatment. These were generally mild-to-moderate and resolved within a median of 4 days. No new types of toxicity were reported. CONCLUSIONS: For patients who meet predefined criteria, retreatment with ipilimumab is generally well tolerated and can translate into clinical benefit. This strategy should be compared with other therapeutic options in randomised controlled trials.


Subject(s)
Antibodies, Monoclonal/therapeutic use , Melanoma/therapy , Skin Neoplasms/therapy , Adult , Aged , Aged, 80 and over , Disease Progression , Female , Health Plan Implementation , Health Services Accessibility , Humans , Immunotherapy/methods , Ipilimumab , Italy , Male , Melanoma/mortality , Melanoma/pathology , Middle Aged , Program Development , Remission Induction , Retreatment , Skin Neoplasms/mortality , Skin Neoplasms/pathology , Survival Analysis , Young Adult
19.
Ann Oncol ; 24(11): 2911-5, 2013 Nov.
Article in English | MEDLINE | ID: mdl-24067719

ABSTRACT

BACKGROUND: Patients with advanced uveal melanoma have a poor prognosis and limited treatment options. Ipilimumab is approved for pre-treated adult patients with advanced melanoma. However, because previous clinical trials with ipilimumab have excluded patients with uveal melanoma, data in this patient population are limited. PATIENTS AND METHODS: Pre-treated patients with advanced uveal melanoma received ipilimumab 3 mg/kg through an expanded access programme, every 3 weeks for four doses. Tumour assessments were conducted at baseline and after completion of treatment and patients were monitored throughout for adverse events. RESULTS: Among 82 assessable patients, 4 (5%) had an immune-related objective response and 24 (29%) had immune-related stable disease lasting ≥3 months for an immune-related disease control rate of 34%. With a median follow-up of 5.6 months, median overall survival (OS) was 6.0 months and median progression-free survival (PFS) was 3.6 months. The 1-year rates of OS and PFS were 31% and 11%, respectively. The safety profile of ipilimumab was similar to that in patients with cutaneous melanoma. CONCLUSIONS: These data suggest ipilimumab 3 mg/kg is a feasible option in pre-treated patients with metastatic uveal melanoma. Evidence of disease control and a 1-year survival rate of 31% indicate the need for further investigation in randomised, controlled trials to determine the optimal timing and use of ipilimumab in this patient population.


Subject(s)
Antibodies, Monoclonal/administration & dosage , Melanoma/drug therapy , Skin Neoplasms/drug therapy , Uveal Neoplasms/drug therapy , Adult , Aged , Aged, 80 and over , Antibodies, Monoclonal/adverse effects , Disease-Free Survival , Female , Humans , Ipilimumab , Male , Melanoma/mortality , Melanoma/pathology , Middle Aged , Neoplasm Metastasis , Neoplasm Staging , Skin Neoplasms/mortality , Skin Neoplasms/pathology , Treatment Outcome , Uveal Neoplasms/mortality , Uveal Neoplasms/pathology
20.
Histol Histopathol ; 27(10): 1327-32, 2012 10.
Article in English | MEDLINE | ID: mdl-22936451

ABSTRACT

The term pseudolymphoma refers to a heterogeneous group of benign reactive T-cell or B-cell lymphoproliferative processes of diverse causes that simulate lymphoma clinically and histologically but usually undergo spontaneous remission. Its pathogenesis is still unclear. The prognosis is good although some evidence suggests that pseudolymphoma may progress to lymphoma. Pseudolymphoma of the urinary tract is extremely rare. We herein report a case of pseudolymphoma of the renal sinus in a 70-year-old man, associated with a high grade urothelial carcinoma of the bladder and to a prostatic adenocarcinoma (Gleason score 6). A brief review of the literature is included. The kidney showed a well-defined, whitish soft mass which involved the renal sinus. Microscopically, the lesion of the renal sinus consisted of a proliferation of small to medium size lymphocytes (CD20 positive and Bcl-2 negative) sometimes arranged in hyperplastic follicular structures. The diagnosis was confirmed by molecular studies which showed an oligopolyclonal IgH rearrangement. To the best of our knowledge, this is the second case of pseudolymphoma with a complete molecular characterization ever described in the renal sinus and the first one associated with multiple urogenital carcinomas.


Subject(s)
Kidney Diseases/complications , Neoplasms, Multiple Primary/complications , Pseudolymphoma/complications , Adenocarcinoma/complications , Aged , Gene Rearrangement, B-Lymphocyte, Heavy Chain , Humans , Kidney Diseases/genetics , Kidney Diseases/immunology , Kidney Diseases/pathology , Male , Neoplasms, Multiple Primary/pathology , Prostatic Neoplasms/complications , Pseudolymphoma/genetics , Pseudolymphoma/immunology , Pseudolymphoma/pathology , Urinary Bladder Neoplasms/complications
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