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1.
Oncology ; 101(4): 234-239, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36538913

RESUMO

BACKGROUND/AIM: Breast angiosarcoma is a rare and aggressive disease with a poor prognosis. Two subtypes have been identified: primary angiosarcoma (PBA) and secondary breast angiosarcoma (SBA). In this retrospective analysis, we describe and compare our institute experience with the data existing in the literature. MATERIALS AND METHODS: We included in our analysis 29 patients who received a diagnosis of PBA or SBA between 2006 and 2019. RESULTS: All patients received surgery as frontline treatment, but only 6 patients underwent to adjuvant treatment. Neoadjuvant chemotherapy was administered 2 patients. The preferred chemotherapeutic regimen was taxanes with or without gemcitabine and associated with anthracyclines. A lower median RFS and OS were reported in patients with PBA compared to those with SBA, but the difference observed was not statistically significant. Patients with PBA had a lower median age at the diagnosis (38 vs. 75). CONCLUSION: In our analysis, we have shown a lower median RFS and OS in patients with PBA compared with those with SBA, and a significantly younger age at diagnosis in patients affected by PBA.


Assuntos
Neoplasias da Mama , Hemangiossarcoma , Humanos , Feminino , Hemangiossarcoma/tratamento farmacológico , Estudos Retrospectivos , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/cirurgia , Antibióticos Antineoplásicos
2.
J Transl Med ; 19(1): 173, 2021 04 26.
Artigo em Inglês | MEDLINE | ID: mdl-33902630

RESUMO

Sarcomas are rare, ubiquitous and heterogeneous tumors usually treated with surgery, chemotherapy, target therapy, and radiotherapy. However, 25-50% of patients experience local relapses and/or distant metastases after chemotherapy with an overall survival about 12-18 months. Recently, immuno-therapy has revolutionized the cancer treatments with initial indications for non-small cell lung cancer (NSCLC) and melanoma (immune-checkpoint inhibitors).Here, we provide a narrative review on the topic as well as a critical description of the currently available trials on immunotherapy treatments in patients with sarcoma. Given the promising results obtained with anti-PD-1 monoclonal antibodies (pembrolizumab and nivolumab) and CAR-T cells, we strongly believe that these new immunotherapeutic approaches, along with an innovative characterization of tumor genetics, will provide an exciting opportunity to ameliorate the therapeutic management of sarcomas.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Sarcoma , Humanos , Imunoterapia , Recidiva Local de Neoplasia , Sarcoma/terapia
3.
BMC Cancer ; 19(1): 899, 2019 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-31500586

RESUMO

BACKGROUND: Combination of chemotherapies (fluoropirimidines, oxaliplatin and irinotecan) with biologic drugs (bevacizumab, panitumumab, cetuximab) have improved clinical responses and survival of metastatic colorectal cancer (mCRC). However, patients' selection thorough the identification of predictive factors still represent a challange. Cetuximab (Erbitux®), a chimeric monoclonal antibody binding to the Epidermal Growth Factor Receptor (EGFR), belongs to the Immunoglobulins (Ig) grade 1 subclass able to elicite both in vitro and in vivo the Antibody-Dependent Cell-mediated Cytotoxicity (ADCC). ADCC is the cytotoxic killing of antibody-coated target cells by immunologic effectors. The effector cells express a receptor for the Fc portion of these antibodies (FcγR); genetic polymorphisms of FcγR modify the binding affinity with the Fc of IgG1. Interestingly, the high-affinity FcγRIIIa V/V is associated with increased ADCC in vitro and in vivo. Thus, ADCC could partially account for cetuximab activity. METHODS/DESIGN: CIFRA is a single arm, open-label, phase II study assessing the activity of cetuximab in combination with irinotecan and fluorouracile in FcγRIIIa V/V patients with KRAS, NRAS, BRAF wild type mCRC. The study is designed with a two-stage Simon model based on a hypothetical higher response rate (+ 10%) of FcγRIIIa V/V patients as compared to previous trials (about 60%) assuming ADCC as one of the possible mechanisms of cetuximab action. The test power is 95%, the alpha value of the I-type error is 5%. With these assumptions the sample for passing the first stage is 14 patients with > 6 responses and the final sample is 34 patients with > 18 responses to draw positive conclusions. Secondary objectives include toxicity, responses' duration, progression-free and overall survival. Furthermore, an associated translational study will assess the patients' cetuximab-mediated ADCC and characterize the tumor microenvironment. DISCUSSION: The CIFRA study will determine whether ADCC contributes to cetuximab activity in mCRC patients selected on an innovative immunological screening. Data from the translational study will support results' interpretation as well as provide new insights in host-tumor interactions and cetuximab activity. TRIAL REGISTRATION: The CIFRA trial (version 0.0, June 21, 2018) has been registered into the NIH-US National Library of Medicine, ClinicalTrials.gov database with the identifier number ( NCT03874062 ).


Assuntos
Cetuximab/uso terapêutico , Neoplasias Colorretais/tratamento farmacológico , Fluoruracila/uso terapêutico , Irinotecano/uso terapêutico , Receptores de IgG/genética , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Colorretais/genética , Neoplasias Colorretais/metabolismo , Humanos , Polimorfismo Genético , Resultado do Tratamento
4.
J Transl Med ; 15(1): 82, 2017 04 26.
Artigo em Inglês | MEDLINE | ID: mdl-28441954

RESUMO

BACKGROUND: Extensive squamous cell carcinoma has few therapeutic options. In such cases, electrochemotherapy involving electroporation combined with antineoplastic drug appears to be a new potential option and may be considered as an alternative treatment. The aim of this retrospective single-center study was to evaluate electrochemotherapy efficacy in treatment of locally advanced stage III squamous cell carcinoma, in which surgical procedures would have entailed wide tissue sacrifice. METHODS: Clinical features, treatment response, and adverse effects were evaluated in 22 patients treated with electrochemotherapy with intravenous injection of bleomycin for extensive stage III cutaneous squamous cell carcinoma. Treatment of cutaneous lesions were performed according to the European Standard Operating Procedures of Electrochemotherapy. RESULTS: Overall response to electrochemotherapy treatment was observed in 18 (81.8%) patients. Clinical response with necrosis of tumor mass was observed from the first session and lasted for all follow up period that ranged between 5 and 48 months with a median of 34 months. Overall the treatment was well tolerated with a very low complication rate. CONCLUSIONS: Electrochemotherapy represents a safe and effective therapeutic approach, associated with a good tolerability.


Assuntos
Carcinoma de Células Escamosas/tratamento farmacológico , Carcinoma de Células Escamosas/patologia , Eletroquimioterapia , Neoplasias Cutâneas/tratamento farmacológico , Neoplasias Cutâneas/patologia , Idoso , Idoso de 80 Anos ou mais , Eletroquimioterapia/efeitos adversos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Estudos Retrospectivos , Resultado do Tratamento
5.
BMC Cancer ; 16(1): 918, 2016 11 25.
Artigo em Inglês | MEDLINE | ID: mdl-27884140

RESUMO

BACKGROUND: Recurrent/metastatic squamous cell carcinoma of the head and neck (SCCHN) has a poor prognosis and the combination of cisplatin and cetuximab, with or without 5-fluorouracil, is the gold standard treatment in this stage. Thus, the concomitant use of novel compounds represents a critical strategy to improve treatment results. Histone deacetylase inhibitors (HDACi) enhance the activity of several anticancer drugs including cisplatin and anti-Epidermal Growth Factor Receptor (anti-EGFR) compounds. Preclinical studies in models have shown that vorinostat is able to down regulate Epidermal Growth Factor Receptor (EGFR) expression and to revert epithelial to mesenchimal transition (EMT). Due to its histone deacetylase (HDAC) inhibiting activity and its safe use as a chronic therapy for epileptic disorders, valproic acid (VPA) has been considered a good candidate for anticancer therapy. A reasonable option may be to employ the combination of cisplatin, cetuximab and VPA in recurrent/metastatic SCCHN taking advantage of the possible positive interaction between histone deacetylase inhibitors, cisplatin and/or anti-EGFR. METHOD/DESIGN: V-CHANCE is a phase 2 clinical trial evaluating, in patients with recurrent/metastatic squamous cell carcinoma of the head and neck never treated with first-line chemotherapy, the concomitant standard administration of cisplatin (on day 1, every 3 weeks) and cetuximab (on day 1, weekly), in combination with oral VPA given daily from day -14 with a titration strategy in each patient (target serum level of 50-100 µg/ml). Primary end point is the objective response rate measured according to Response Evaluation Criteria in Solid Tumors (RECIST). Sample size, calculated according to Simon 2 stage minimax design will include 21 patients in the first stage with upper limit for rejection being 8 responses, and 39 patients in the second stage, with upper limit for rejection being 18 responses. Secondary endpoints are time to progression, duration of response, overall survival, safety. Objectives of the translational study are the evaluation on tumor samples of markers of treatment efficacy/resistance (i.e. γH2AX, p21/WAF, RAD51, XRCC1, EGFR, p-EGFR, Ki-67) and specific markers of VPA HDAC inhibitory activity (histones and proteins acetylation, Histone deacetylase isoforms) as well as valproate test, histones and proteins acetylation of peripheral blood mononuclear cell, tested on blood samples at baseline and at different time points during treatment. DISCUSSION: Overall, this study could provide a less toxic and more effective first-line chemotherapy regimen in patients with recurrent/metastatic squamous cell carcinoma of the head and neck by demonstrating the feasibility and efficacy of cisplatin/cetuximab plus valproic acid. Moreover, correlative studies could help to identify responder patients, and will add insights in the mechanism of the synergistic interaction between these agents. EUDRACT NUMBER: 2014-001523-69 TRIAL REGISTRATION: ClinicalTrials.gov number, NCT02624128.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Carcinoma de Células Escamosas/tratamento farmacológico , Cetuximab/administração & dosagem , Cisplatino/administração & dosagem , Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Recidiva Local de Neoplasia/tratamento farmacológico , Ácido Valproico/administração & dosagem , Administração Oral , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Cetuximab/uso terapêutico , Cisplatino/uso terapêutico , Esquema de Medicação , Feminino , Humanos , Masculino , Metástase Neoplásica , Recidiva Local de Neoplasia/patologia , Carcinoma de Células Escamosas de Cabeça e Pescoço , Análise de Sobrevida , Resultado do Tratamento , Ácido Valproico/uso terapêutico
6.
Biology (Basel) ; 12(9)2023 Aug 29.
Artigo em Inglês | MEDLINE | ID: mdl-37759584

RESUMO

Cancer manifests as a multifaceted disease, characterized by aberrant cellular proliferation, survival, migration, and invasion. Tumors exhibit variances across diverse dimensions, encompassing genetic, epigenetic, and transcriptional realms. This heterogeneity poses significant challenges in prognosis and treatment, affording tumors advantages through an increased propensity to accumulate mutations linked to immune system evasion and drug resistance. In this review, we offer insights into tumor heterogeneity as a crucial characteristic of cancer, exploring the difficulties associated with measuring and quantifying such heterogeneity from clinical and biological perspectives. By emphasizing the critical nature of understanding tumor heterogeneity, this work contributes to raising awareness about the importance of developing effective cancer therapies that target this distinct and elusive trait of cancer.

7.
Cells ; 12(12)2023 06 15.
Artigo em Inglês | MEDLINE | ID: mdl-37371106

RESUMO

Dacarbazine is an important drug in the therapeutic landscape of leiomyosarcoma (LMS). Alkylating agents are subjected to resistance mechanisms based on anti-apoptotic pathways and repair mechanisms, including the DNA repair enzyme O6-methylguanine-DNA methyltransferase (MGMT). In this retrospective study, the methylation status of the MGMT promoter in histological tumor samples from patients with LMS, dacarbazine-based regimens-treated, was measured and correlated with clinical outcomes aimed at optimizing the use of dacarbazine in soft tissue sarcomas. The patients with unmethylated MGMT had better outcomes than those with methylated MGMT. Patients without MGMT methylation had better Progression Free Survival (PFS) when aged ≥62 years compared to those aged <62 years, while PFS of patients with methylated MGMT was less favorable independently of age (p = 0.0054). The patients without a methylated MGMT gene had higher Disease control rate (DCR). These results are not in agreement with the role of the methylated MGMT gene in other tumors, and with this study, we demonstrated the correlation between methylated MGMT and poor prognosis; despite that, sample smallness, heterogeneity of LMS and of treatment history could be selection bias. Predictive markers of response to chemotherapies in sarcomas remain an unmet need.


Assuntos
Neoplasias Encefálicas , Leiomiossarcoma , Humanos , Antineoplásicos Alquilantes/farmacologia , Antineoplásicos Alquilantes/uso terapêutico , Neoplasias Encefálicas/patologia , Dacarbazina/uso terapêutico , DNA , Metilação de DNA/genética , Metilases de Modificação do DNA/genética , Metilases de Modificação do DNA/uso terapêutico , Enzimas Reparadoras do DNA/genética , Leiomiossarcoma/tratamento farmacológico , Leiomiossarcoma/genética , Metiltransferases/genética , Estudos Retrospectivos , Temozolomida/farmacologia , Temozolomida/uso terapêutico , Proteínas Supressoras de Tumor/genética , Pessoa de Meia-Idade
8.
J Clin Med ; 11(10)2022 May 12.
Artigo em Inglês | MEDLINE | ID: mdl-35628872

RESUMO

PURPOSE: Surgery, radiotherapy, and oncological treatment (chemotherapy and antineoplastic antibodies) are standard treatments of rectal cancer. ECT has shown its effectiveness and suitability in deep solid tumors conducted in both preclinical and clinical studies. We show here an update and preliminary results with locally advanced rectum cancer (LARC) treated with ECT. METHODS: Two patients with major clinical response to restaging after neoadjuvant treatment for LARC were subjected to ECT 12 weeks after completing chemo-radiation therapy. One patient was subjected to ECT on a colorectal local recurrence formed after neoadjuvant treatment for LARC and surgery. Computed Tomography and Magnetic Resonance Imaging were used to assess ECT response. RESULTS: The results showed stable disease in two of the three patients treated, while one patient achieved a complete response. The local control of disease is maintained in the patient follow-up. For each patient, a reduction in pain was observed and for the patient with local recurrence, a reduction in bleeding present before ECT was also achieved. CONCLUSION: Preliminary results showed that ECT is a safe and effective treatment in patients with a major clinical response or local recurrence after neoadjuvant therapy for LARC and allows a reduction in pain and bleeding with a consequent improvement to quality of life.

9.
Cancers (Basel) ; 13(16)2021 Aug 10.
Artigo em Inglês | MEDLINE | ID: mdl-34439171

RESUMO

Retroperitoneal sarcomas (RPS) are rare cancers whose management can be challenging due to various presentation patterns, multiple organ involvement, and a high local and distant recurrence rate. Histopathology and prognostic factors analysis are essential to predict the behaviour of the disease and plan the best therapeutic strategy. To date, surgery is still the main therapeutic option that guarantees a chance of cure from the primary disease. While chemotherapy and radiotherapy seem to be good options for controlling metastatic and recurrent irresectable disease, their role in the treatment of primary RPS remains unclear. This literature review aims to provide a comprehensive overview of the multidisciplinary aspects of RPS management in high-volume centres, summarising the diagnostic path, the prognostic factors, and the most suitable therapeutic options.

10.
Cancers (Basel) ; 13(13)2021 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-34206858

RESUMO

BACKGROUND: Currently, 45-55% of rectal cancer patients receive preoperative chemo- radio-therapy for Locally Advanced Rectal Cancer (LARC). The idea of our study is to use Electrochemotherapy (ECT) before surgery, in patients with major clinical response after neoadjuvant therapy, to allow for a more conservative surgical approach. OBJECTIVE: To evaluate the increase of the complete response rate after neoadjuvant treatment in LARC and to spare organ function due to total mesorectal excision (TME). PATIENTS AND METHODS: This is a Phase II randomized controlled trial enrolling 70 patients that will be developed in two stages. In the first step, 28 patients will be enrolled: 14 of these will receive ECT for four weeks after neo-adjuvant treatment and then local excision (treatment group) and 14 patients will receive neo-adjuvant treatment and then local excision (control group). If an increase of response rate is observed in the first stage, and/or feasibility/safety is demonstrated, the second stage of the trial will be performed, enrolling an additional 42 patients. The treatment response. in both the control arm and the treatment arm, will be assessed using the histopathological tumor regression grade on tissue specimens after local excision.

11.
Exp Ther Med ; 22(5): 1298, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34630653

RESUMO

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for the recent Coronavirus Disease 2019 (COVID-19) pandemic, which has spread all over the world over the past year. Comorbidities appear to affect the prognosis of patients with such diseases, but the impact of cancer on the course of SARS-CoV2 has remained largely elusive. The aim of the present study is to analyze the outcome of patients affected by squamous cell carcinoma of the head and neck (SCCHN) and a number of their comorbidities, if infected with SARS-CoV2. The clinical data of 100 patients affected by SCCHN, who were undergoing treatment or who had finished their oncologic treatment in the past 6 months, were retrospectively collected and analysed. For each patient, the Charlson Comorbidity Index (CCI) was calculated to provide a score assessing the real weight of comorbidities on the patient's outcome at the time of diagnosis. It was discovered that these patients, besides the SCCHN, frequently presented at diagnosis with several other comorbidities, including hypertension, type 2 diabetes, cardiac arrhytmia, chronic obstructive pulmonary disease and various forms of vasculopathy (and thus a poor CCI). This feature suggest that, given the high frequency of various comorbidities in patients with SCCHN, additional SARS-CoV2 infection could have particularly devastating consequences.

12.
Ther Adv Med Oncol ; 13: 1758835921989223, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33854566

RESUMO

BACKGROUND: The intensive study of predictive factors has strongly ameliorated the therapeutic flow-chart of metastatic colorectal cancer (mCRC) by allowing the selection of patients who benefit from specific therapies. For instance, in mRAS (mutated RAS) mCRC patients, anti-EGFR drugs (cetuximab and panitumumab) are not recommended; in this group of patients, the use of anti-angiogenic drugs (bevacizumab and aflibercept) is predominant. However, at progression to standard bevacizumab-based first-line chemotherapy, still to date, there are no studies to guide oncologists in the choice of the best second-line anti-angiogenic drug (bevacizumab beyond progression versus aflibercept). METHODS: ARBITRATION is a prospective, observational study assessing efficacy differences between second-line fluorouracil/irinotecan (FOLFIRI)/bevacizumab versus FOLFIRI/aflibercept at progression to fluoropyrimidines, oxaliplatin and bevacizumab in mRAS mCRC patients. A test power of 80%, a median survival of 9 months from second-line treatment start and a hazard ratio of 0.67 between the two schedules were the basis for statistical design. The final sample will be 220 patients (110 per treatment). The significance will be verified with a two-tailed log-rank test with an alpha value of the I-type error of 5%. Time-to-outcome will be described by Kaplan-Meier curves and prognostic factors studied through multivariable analyses based on the Cox model. Secondary objectives include safety, responses' duration and progression-free survival. A translational research will be conducted to measure several angiogenic proteins in patients' serum before starting the therapy in order to evidence any angiogenic factor patterns related to outcome. DISCUSSION: We present a large, prospective, observational study aiming to answer two scientific questions: (1) outcome differences between second-line treatments with FOLFIRI/bevacizumab beyond progression versus FOLFIRI/aflibercept in mRAS mCRC patients, (2) angiogenic factors' patterns that could associate with efficacy and help oncologists to apply best the therapeutic anti-angiogenic strategies. TRIAL REGISTRATION: The ARBITRATION trial (version 0.0, 13 April 2020) has been registered into the clinicaltrials.gov registry on 20 May 2020 with identifier NCT04397601.

13.
Onco Targets Ther ; 13: 1179-1184, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32110037

RESUMO

PURPOSE: To describe the outcome of a patient with a rare primitive uterine pPNET and to perform a review of the available data in literature, leading the clinicians to better face this rare disease. METHODS: We have rescued data regarding the multidisciplinary treatment of pPNET from the PUBMED database, highlighting also issues regarding the pathogenesis and the genetic landscape of the ESFTs (Ewing Sarcoma Family of Tumors). RESULTS: Ewing sarcoma and primitive neuroectodermal tumors (PNETs) are small round cell tumors presenting with different degrees of neuroectodermal differentiation. PNETs are further divided into central PNET and peripheral PNET (pPNET). Since pPNETs share the same genetic background of Ewing Sarcomas, they are considered to belong to the Ewing Sarcoma Family of Tumors (ESFTs). Multimodality treatment currently represents the best choice to offer to the affected patients. CONCLUSION: Although pPNETs are generally diagnosed in children and young adults, an elderly woman aged 85 years came to our attention after a diagnosis of uterine pPNET. Her medical history is presented here, along with a literature review of the subject, highlighting the main biological, pathological and clinical features, with a hypothesis about the possible future therapeutic approaches for these rare malignancies.

14.
Jpn J Radiol ; 36(10): 611-621, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30039258

RESUMO

PURPOSE: To investigate the potential of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) to discriminate responder from non-responder patients after preoperative chemoradiotherapy (pCRT) in locally advanced rectal cancer (LARC). MATERIALS AND METHODS: One hundred and fifty-eight consecutive patients were enrolled in this prospective study. We compared morphological MRI (mMRI) using T2-weighted images about tumor presence and invasiveness, and functional DCE-MRI using time-intensity curve (TIC) visual inspection (qMRI), classifying TIC shape into three types: type 1, persistent enhancement; type 2, high enhancement with plateau; type 3, high enhancement with wash-out. Clinical TNM was obtained before and after CRT by radiological consensus of two expert radiologists. Pathological tumor-nodes-metastasis classification and tumor regression grade (TRG) were confirmed as the golden standard. Non-parametric test, sensitivity, specificity, and positive and negative predictive values were calculated. RESULTS: Ninety-eight patients (62%) were classified as responders (TRG ≤ 2), while 60 (38%) were classified as non-responders. Sensitivity, specificity, and accuracy were 52, 78, and 62% for mMRI, and 81, 85, and 82% for qMRI, respectively. CONCLUSIONS: TIC visual inspection may be one of the potential biomarkers over morphological analysis using DCE-MRI data to assess pathological response after pCRT in LARC.


Assuntos
Meios de Contraste , Aumento da Imagem/métodos , Imageamento por Ressonância Magnética/métodos , Terapia Neoadjuvante/métodos , Neoplasias Retais/diagnóstico por imagem , Neoplasias Retais/terapia , Adulto , Idoso , Quimiorradioterapia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Reto/diagnóstico por imagem , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Resultado do Tratamento
15.
Eur Radiol Exp ; 1(1): 10, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29708202

RESUMO

BACKGROUND: In breast magnetic resonance imaging (MRI) analysis for lesion detection and classification, radiologists agree that both morphological and dynamic features are important to differentiate benign from malignant lesions. We propose a multiple classifier system (MCS) to classify breast lesions on dynamic contrast-enhanced MRI (DCE-MRI) combining morphological features and dynamic information. METHODS: The proposed MCS combines the results of two classifiers trained with dynamic and morphological features separately. Twenty-six malignant and 22 benign breast lesions, histologically proven, were analysed. The lesions were subdivided into two groups: training set (14 benign and 18 malignant) and testing set (8 benign and 8 malignant). Volumes of interest were extracted both manually and automatically. We initially considered a feature set including 54 morphological features and 98 dynamic features. These were reduced by means of a selection procedure to delete redundant parameters. The performance of each of the two classifiers and of the overall MCS was compared with pathological classification. RESULTS: We obtained an accuracy of 91.7% on the testing set using automatic segmentation and combining the best classifier for morphological features (decision tree) and for dynamic information (Bayesian classifier). With implementation of the MCS, an increase in accuracy of 12.5% and of 31.3% was obtained compared with the accuracy of the Bayesian classifier tested with dynamic features and with that of the decision tree tested with morphological parameters, respectively. CONCLUSIONS: An MCS can optimise the accuracy for breast lesion classification combining morphological features and dynamic information.

16.
BMC Res Notes ; 8: 147, 2015 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-25890364

RESUMO

BACKGROUND: Primary umbilical melanoma is an uncommon tumor that is poorly described in the medical literature. The umbilical region is a particular anatomic site owing to the presence of embryonal remnants, which can be a potential metastatic pathway, as well as the braided lymphatic network drainage. Hence, primary malignant neoplasms affecting the umbilicus require a different and more radical surgical approach compared with other melanomas. CASE PRESENTATION: In this report, we describe a series of three patients of Caucasian ethnicity who presented with primary umbilical melanoma at the National Cancer Institute of Naples, Italy. All patients underwent wide excision of the tumor including the underlying peritoneum. No surgical complications, either immediate or delayed, were observed in any of the patients. Sentinel lymph node biopsy was negative in two cases. Two of the patients developed metastatic disease and died after systemic medical therapy. The other patient is currently in follow-up, and remains disease-free after 21 months. CONCLUSIONS: The umbilicus has vascular and embryological connections with the underlying peritoneum, so that early visceral involvement is more likely to occur with primary umbilical melanomas. As such, tumor resection including the underlying peritoneum is required to avoid local relapse, whilst sentinel lymph node biopsy appears to be of poor diagnostic value.


Assuntos
Melanoma/cirurgia , Peritônio/cirurgia , Neoplasias Cutâneas/cirurgia , Umbigo/cirurgia , Adulto , Idoso , Feminino , Humanos , Linfonodos/patologia , Linfonodos/cirurgia , Metástase Linfática , Masculino , Melanoma/patologia , Pessoa de Meia-Idade , Peritônio/patologia , Biópsia de Linfonodo Sentinela , Neoplasias Cutâneas/patologia , Umbigo/patologia
17.
Oncoimmunology ; 4(6): e1008842, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-26155423

RESUMO

Melanoma is responsible for most skin cancer-related deaths and is one of the most common cancers diagnosed in young adults. In melanoma, tumors can become established by activation of the negative regulator of cytotoxic T lymphocytes (CTLs), CTL antigen-4 (CTLA-4). Ipilimumab blocks the interaction of CTLA-4 with CD80/CD86 and augments T-cell activation and proliferation. In electrochemotherapy (ECT), local application of short high-voltage pulses renders cell membranes transiently permeable to chemotherapeutic drugs. The combination of ipilimumab and ECT may be beneficial for the treatment of metastatic melanoma; however, no prospective data are available to date. Here, we report the retrospective analysis of patients treated with ipilimumab in an expanded access program (EAP) who also received ECT. Fifteen patients with previously treated metastatic melanoma who received ipilimumab 3 mg/kg every three weeks for four cycles and underwent ECT for local disease control and/or palliation of cutaneous lesions with bleomycin 15 mg/m2 after the first ipilimumab infusion were included in the analysis. Over the study period, a local objective response was observed in 67% of patients (27% complete response [CR] and 40% partial response [PR]). According to immune-related response criteria, a systemic response was observed in nine patients (five PR and four stable disease [SD]), resulting in a disease control rate of 60%. Evaluation of circulating T-regulatory (T-reg) cells demonstrated significant differences between responders and non-responders. Overall, treatment was well-tolerated and without notable toxicity. In conclusion, the combination of ipilimumab and ECT appears to be beneficial to patients with advanced melanoma, warranting further investigation in prospective trials.

18.
Curr Med Res Opin ; 24(4): 1011-5, 2008 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-18291065

RESUMO

BACKGROUND: The haemostatic matrix (FloSeal) is a topical agent that provides effective haemostasis in a range of surgical applications. We evaluated this sealant for intraoperative haemostatic effectiveness in an observational series of patients undergoing surgery for the resection of primary and metastatic liver tumours. METHODS: A haemostatic matrix was applied directly to areas of bleeding. The severity of bleeding before and after application was graded on a 5-point scale (0 = no bleeding, 1 = oozing, 2 = moderate blood flow, 3 = heavy blood flow, 4 = spurting blood). The time to complete haemostasis was also recorded. RESULTS: 105 women (age 61 +/- 9 years) and 132 men (age 61 +/- 12 years) were included in this study. One hundred and seventeen patients (49.36%) had pre-operative coagulopathy resulting from co-existent cirrhosis (67 Child-Pugh Class A; 50 Child-Pugh Class B). Prior to administration of a haemostatic matrix, 93 bleeding sites (24.8%) had a bleeding severity score of 2, 269 bleeding sites (71.7%) had a score of 3 and 13 bleeding sites (3.5%) had a score of 4. Following administration of the haemostatic matrix, bleeding stopped completely (score of 0) at 367 (97.9%) of the 375 sites and was reduced to a score of 1 at the remaining 8 sites (2.1%), of which only 2 were in patients with coagulopathy. The mean time to achieve haemostasis in the overall population was 2.9 +/- 1 min; this was significantly increased in patients with coagulopathy versus noncoagulopathic patients (4 +/- 1 vs. 2 +/- 1 min, p < 0.001). CONCLUSIONS: In this prospective, uncontrolled study of 237 consecutive patients undergoing major hepatic surgery to remove primary or metastatic tumours, application of a haemostatic matrix provided rapid and effective intraoperative control of mild to severe bleeding from the liver edge, even in patients with prolonged bleeding times resulting from cirrhosis. This preliminary evidence warrants a randomised, controlled clinical trial with a larger sample size.


Assuntos
Perda Sanguínea Cirúrgica/prevenção & controle , Hemostasia/efeitos dos fármacos , Hepatectomia/métodos , Neoplasias Hepáticas/cirurgia , Hemorragia Pós-Operatória/prevenção & controle , Trombina/administração & dosagem , Feminino , Géis , Humanos , Itália , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Fatores de Tempo
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