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1.
Eur Rev Med Pharmacol Sci ; 26(16): 5902-5910, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-36066165

RESUMO

OBJECTIVE: In the hybrid Positron Emission Tomography/Computed Tomography (PET/CT) method, the functional evaluation is integrated with the morphological information provided by co-registered CT, still performed for attenuation correction and lesion localization. However, co-registered CT images could provide additional diagnostic information that PET alone could underestimate. To optimize the diagnostic potential of this hybrid examination, we evaluated the prevalence and the clinical significance of incidental findings detected on co-registered CT images in a cohort of multiple myeloma (MM) patients. PATIENTS AND METHODS: We evaluated 112 MM patients (mean age 65.8 y), who underwent [18F]FDG-PET/CT during their regular workup. All co-registered CT images were retrospectively reviewed by two expert radiologists and each non-myelomatous incidental finding (nM-IF) was collected and clinically graded according to a nM-IF Reporting and Data System (nM-RADS). In addition, nM-IFs were classified according to anatomic localization (skull, lung, mediastinum, abdomen, breast, gastrointestinal, genitourinary and cardiovascular system and muscle/soft tissue). RESULTS: 163 nM-IFs were detected in 94/112 patients (83.9%) (mean value: 1.5 IFs per patient). The most interested anatomic districts were the lung (n=33; 20.2%), genitourinary (n=33; 20.2%) and gastrointestinal (n=30; 18.4%) systems. Focusing on the clinically significant findings (nM3+nM4), 92/163 (56.4%) IFs could have been required further investigations, of which 38/163 (23.3%) were potentially important and detected in 33/112 (29.5%) patients. CONCLUSIONS: The high percentage of potentially clinically significant IFs detected in MM patients emphasizes that co-registered CT images hold precious information often missed. Giving more relevance to co-registered CT with tailored acquisition and reconstruction protocols and dedicated reporting could optimize the potentiality of this multimodality imaging method with impact on clinical management.


Assuntos
Mieloma Múltiplo , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Idoso , Fluordesoxiglucose F18 , Humanos , Achados Incidentais , Mieloma Múltiplo/diagnóstico por imagem , Mieloma Múltiplo/epidemiologia , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Tomografia por Emissão de Pósitrons/métodos , Prevalência , Compostos Radiofarmacêuticos , Estudos Retrospectivos , Tomografia Computadorizada por Raios X/métodos
2.
Int J Surg Case Rep ; 79: 405-408, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33517214

RESUMO

INTRODUCTION: Squamous carcinoma is a very rare breast cancer resulting from a differentiated squamous metaplasia. Its diagnosis is late due to the absence of specific clinical and radiological features. PRESENTATION OF CASE: The authors present the case of a 39-year-old patient with the clinical onset of an inflammatory cyst diagnosed with mammography and cytological examination. After segmentectomy, on histological examination was defined as: "squamous keratinizing aspect". In light of this report she was subjected to quadrantectomy with lymphadenectomy. She did not undergo radiotherapy treatment, which was delayed due to the ongoing pandemic. After a few months developed a local recurrence and underwent a mastectomy with multidisciplinary treatment. DISCUSSION: Squamously-differentiated metaplastic carcinoma of the breast is one of the rarest forms of breast cancer. Its etiopathogenesis is still unclear but some authors suggest that it originates from a squamous metaplasia deriving from the epithelium of cysts. This is a very aggressive and fast-growing tumour especially in young women, in fact the patient had a recurrence after a few months. She came to our attention 6 months after the initial surgery with a relapse at a local-regional level for which she was subjected to radical treatment and with a metastatic spread for which she was given the first-line chemotherapy treatment. CONCLUSION: There are no well-defined guidelines for the treatment of this rare form of cancer. The case illustrates how the rapid aggressiveness of the disease requires adequate and immediate multidisciplinary treatment from the very beginning.

3.
Phys Med ; 64: 1-9, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31515007

RESUMO

BACKGROUND: Microcalcification clusters in mammograms can be considered as early signs of breast cancer. However, their detection is a very challenging task because of different factors: large variety of breast composition, highly textured breast anatomy, impalpable size of microcalcifications in some cases, as well as inherent low contrast of mammograms. Thus, the need to support the clinicians' work with an automatic tool. METHODS: In this work a three-phases approach for clustered microcalcification detection is presented. Specifically, it is made up of a pre-processing step, aimed at highlighting potentially interesting breast structures, followed by a single microcalcification detection step, based on Hough transform, that is able to grasp the innate characteristic shape of the structures of interest. Finally, a cluster identification step to group microcalcifications is carried out by means of a clustering algorithm able to codify expert domain rules. RESULTS: The detection performance of the proposed method has been evaluated on 364 mammograms of 182 patients obtaining a true positive ratio of 91.78% with 2.87 false positives per image. CONCLUSIONS: Experimental results demonstrated that the proposed method is able to detect microcalcification clusters in digital mammograms showing performance comparable to different methodologies exploited in the state-of-art approaches, with the advantage that it does not require any training phase and a large set of data. The performance of the proposed approach remains high even for more difficult clinical cases of mammograms of young women having high-density breast tissue thus resulting in a reduced contrast between microcalcifications and surrounding dense tissues.


Assuntos
Calcinose/diagnóstico por imagem , Diagnóstico por Computador/métodos , Mamografia/métodos , Adulto , Idoso , Algoritmos , Automação , Neoplasias da Mama/complicações , Neoplasias da Mama/diagnóstico por imagem , Calcinose/complicações , Reações Falso-Positivas , Feminino , Humanos , Processamento de Imagem Assistida por Computador , Pessoa de Meia-Idade
4.
Ann Oncol ; 30(5): 774-780, 2019 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-30860570

RESUMO

BACKGROUND: BEECH investigated the efficacy of capivasertib (AZD5363), an oral inhibitor of AKT isoforms 1-3, in combination with the first-line weekly paclitaxel for advanced or metastatic estrogen receptor-positive (ER+)/human epidermal growth factor receptor 2-negative (HER2-) breast cancer, and in a phosphoinositide 3-kinase, catalytic, alpha polypeptide mutation sub-population (PIK3CA+). PATIENTS AND METHODS: BEECH consisted of an open-label, phase Ib safety run-in (part A) in 38 patients with advanced breast cancer, and a randomised, placebo-controlled, double-blind, phase II expansion (part B) in 110 women with ER+/HER2- metastatic breast cancer. In part A, patients received paclitaxel 90 mg/m2 (days 1, 8 and 15 of a 28-day cycle) with capivasertib taken twice daily (b.i.d.) at two intermittent ascending dosing schedules. In part B, patients were randomly assigned, stratified by PIK3CA mutation status, to receive paclitaxel with either capivasertib or placebo. The primary end point for part A was safety to recommend a dose and schedule for part B; primary end points for part B were progression-free survival (PFS) in the overall and PIK3CA+ sub-population. RESULTS: Capivasertib was well tolerated, with a 400 mg b.i.d. 4 days on/3 days off treatment schedule selected in part A. In part B, median PFS in the overall population was 10.9 months with capivasertib versus 8.4 months with placebo [hazard ratio (HR) 0.80; P = 0.308]. In the PIK3CA+ sub-population, median PFS was 10.9 months with capivasertib versus 10.8 months with placebo (HR 1.11; P = 0.760). Based on the Common Terminology Criteria for Adverse Event v4.0, the most common grade ≥3 adverse events in the capivasertib group were diarrhoea, hyperglycaemia, neutropoenia and maculopapular rash. Dose intensity of paclitaxel was similar in both groups. CONCLUSIONS: Capivasertib had no apparent impact on the tolerability and dose intensity of paclitaxel. Adding capivasertib to weekly paclitaxel did not prolong PFS in the overall population or PIK3CA+ sub-population of ER+/HER2- advanced/metastatic breast cancer patients.ClinicalTrials.gov: NCT01625286.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/genética , Classe I de Fosfatidilinositol 3-Quinases/genética , Proteínas Proto-Oncogênicas c-akt/antagonistas & inibidores , Receptores de Estrogênio/metabolismo , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Biomarcadores Tumorais/genética , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Classe I de Fosfatidilinositol 3-Quinases/metabolismo , Método Duplo-Cego , Feminino , Humanos , Mutação , Metástase Neoplásica , Recidiva Local de Neoplasia/tratamento farmacológico , Recidiva Local de Neoplasia/genética , Recidiva Local de Neoplasia/metabolismo , Recidiva Local de Neoplasia/patologia , Paclitaxel/administração & dosagem , Paclitaxel/efeitos adversos , Pirimidinas/administração & dosagem , Pirimidinas/efeitos adversos , Pirróis/administração & dosagem , Pirróis/efeitos adversos , Taxa de Sobrevida
5.
G Chir ; 40(1): 44-48, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30771798

RESUMO

Amyand's hernia consists in the protrusion of the vermiform appendix into an inguinal hernia sac and represents an uncommon condition with a difficult preoperative diagnosis to be recognized with clinical examination and imaging diagnostic tools in order to choose a correct therapeutic approach for the patient. Four types of Amyand's hernias exist. The case of a recurrent type 1 Amyand's hernia is presented. Multi detector computed tomography allowed a correct diagnosis and the subsequent surgical treatment had no complication for the patient. Radiologists and surgeons need to be aware of this pathology and its classification, as well as of the importance of recognizing both the inflamed and normal appendix within the inguinal canal and the abdominal complications. With the availability of multi detector CT scanning, a greater number of type 1 and 2 hernias are able to be preoperatively diagnosed, and type 3 and 4 better characterized in emergency situation, allowing to perform the best surgical treatment and reducing the chances of pathological recurrence.


Assuntos
Apêndice/diagnóstico por imagem , Doenças do Ceco/diagnóstico por imagem , Hérnia Inguinal/diagnóstico por imagem , Tomografia Computadorizada Multidetectores , Doenças Raras/diagnóstico por imagem , Idoso , Hérnia Inguinal/complicações , Humanos , Achados Incidentais , Masculino , Recidiva
6.
G Chir ; 39(1): 63-66, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29549684

RESUMO

Lipomas of the digestive tract are rare benign tumours which, in most cases, are totally asymptomatic. Because of their localization within the intestinal wall, endoscopy may be completely negative so contrast-enhanced computed tomography (CT) is very important for detecting and typing these lesions. The case of a 49-year-old man with abdominal pain is presented. Colonoscopy and biopsy of a polypoid lesion on the right colonic flexure concluded for tubulovillous adenoma. The subsequent CT showed a polylobate lesion of 5 cm in diameter with predominant fat density causing luminal sub-stenosis. Histological examination of the surgical specimen confirmed the presence of a voluminous submucosal lipoma. CT allows to diagnose lipomas of the large bowel thanks to the density measurement (between -40 and -120 Hunsfield Units) with an accurate detection of the site and nature of lumen stenosis.


Assuntos
Adenoma Viloso/cirurgia , Neoplasias do Colo/cirurgia , Lipoma/cirurgia , Neoplasias Primárias Múltiplas/cirurgia , Dor Abdominal/etiologia , Adenoma Viloso/diagnóstico por imagem , Adenoma Viloso/patologia , Biópsia , Colectomia/métodos , Neoplasias do Colo/diagnóstico por imagem , Neoplasias do Colo/patologia , Colonoscopia , Humanos , Lipoma/diagnóstico por imagem , Lipoma/patologia , Masculino , Pessoa de Meia-Idade , Neoplasias Primárias Múltiplas/diagnóstico por imagem , Neoplasias Primárias Múltiplas/patologia , Tomografia Computadorizada por Raios X
7.
Curr Oncol ; 25(1): e90-e94, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-29507500

RESUMO

Chemotherapy remains the mainstay of treatment for advanced pancreatic ductal adenocarcinoma (pda). Two randomized trials have demonstrated superiority of the combination regimens folfirinox (5-fluorouracil, leucovorin, oxaliplatin, and irinotecan) and gemcitabine plus nab-paclitaxel over gemcitabine monotherapy as a first-line treatment in adequately fit subjects. Selected pda patients progressing to first-line therapy can receive secondline treatment with moderate clinical benefit. Nevertheless, the optimal algorithm and the role of combination therapy in second-line are still unclear. Published second-line pda clinical trials enrolled patients progressing to gemcitabine-based therapies in use before the approval of nab-paclitaxel and folfirinox. The evolving scenario in second-line may affect the choice of the first-line treatment. For example, nanoliposomal irinotecan plus 5-fluouracil and leucovorin is a novel second-line option which will be suitable only for patients progressing to gemcitabine-based therapy. Therefore, clinical judgement and appropriate patient selection remain key elements in treatment decision. In this review, we aim to illustrate currently available options and define a possible algorithm to guide treatment choice. Future clinical trials taking into account sequential treatment as a new paradigm in pda will help define a standard algorithm.

8.
G Chir ; 38(5): 239-242, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29280704

RESUMO

Pneumatosis cystoides intestinalis (PCI) is a rare disease characterized by the presence of multiple gas-filled cysts within the submucosa or subserosa of the intestinal wall. We report a case of PCI in a 54-yearold man 4 weeks after liver transplantation due to hepatitis B virus (HBV)-associated liver cirrhosis presenting with illness, diarrhea and abdominal pain. CT scans revealed normal shape of the abdominal parenchymal organs and no intra-hepatic complication due to liver transplantation. Main abdominal venous and arterial vessels resulted patent. Colic loops appeared diffusely thickened for the presence of variable diameter air-filled cysts located within the bowel wall. The patient underwent conservative treatment and the CT control after 4 weeks showed a complete PCI resolution. PCI after adult liver transplantation is probably due to the pre-transplantation chemotherapy, immunosuppressive therapy and opportunistic enteric infections. Abdominal CT represents the gold standard technique for diagnosing PCI and for evaluating its extension and complications providing data on other abdominal pathologies. It appears as variable diameter gas-filled cysts located within the bowel wall and it is often associated with pneumo-peritoneum probably due to the rupture of subserosal cysts. PCI has a favorable outcome and requires conservative treatment. Major differential diagnosis includes intestinal pneumatosis due to bowel ischemia. PCI after liver transplantation represents an uncommon bowel disease with a favorable prognosis. CT represents the reference imaging technique for diagnosing the disease and evaluating the response to therapy which is usually conservative rather than surgical.


Assuntos
Transplante de Fígado , Pneumatose Cistoide Intestinal , Complicações Pós-Operatórias , Humanos , Masculino , Pessoa de Meia-Idade , Pneumatose Cistoide Intestinal/diagnóstico por imagem , Complicações Pós-Operatórias/diagnóstico por imagem , Tomografia Computadorizada por Raios X
9.
Leukemia ; 31(11): 2426-2434, 2017 11.
Artigo em Inglês | MEDLINE | ID: mdl-28344315

RESUMO

The extracellular matrix (ECM) is a major component of the tumor microenvironment, contributing to the regulation of cell survival, proliferation, differentiation and metastasis. In multiple myeloma (MM), interactions between MM cells and the bone marrow (BM) microenvironment, including the BM ECM, are critical to the pathogenesis of the disease and the development of drug resistance. Nevertheless, composition of the ECM in MM and its role in supporting MM pathogenesis has not been reported. We have applied a novel proteomic-based strategy and defined the BM ECM composition in patients with monoclonal gammopathy of undetermined significance (MGUS), newly diagnosed and relapsed MM compared with healthy donor-derived BM ECM. In this study, we show that the tumor ECM is remodeled at the mRNA and protein levels in MGUS and MM to allow development of a permissive microenvironment. We further demonstrate that two ECM-affiliated proteins, ANXA2 and LGALS1, are more abundant in MM and high expression is associated with a decreased overall survival. This study points to the importance of ECM remodeling in MM and provides a novel proteomic pipeline for interrogating the role of the ECM in cancers with BM tropism.


Assuntos
Medula Óssea/metabolismo , Matriz Extracelular/metabolismo , Mieloma Múltiplo/metabolismo , Proteoma , Anexina A2/metabolismo , Estudos de Casos e Controles , Galectina 1/metabolismo , Perfilação da Expressão Gênica , Humanos , Mieloma Múltiplo/genética , Mieloma Múltiplo/patologia , Análise de Sobrevida , Microambiente Tumoral
10.
Vet Comp Oncol ; 15(4): 1572-1584, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28322030

RESUMO

BACKGROUND: Melatonin has oncostatic actions and IL-25 is active in inflammatory processes that induce apoptosis in tumor cells AIM: The aim of this study was to evaluate melatonin and IL-25 in metastatic (CF-41) and non-metastatic (CMT-U229) canine mammary tumor cells cultured as monolayers and tridimensional structures. MATERIALS AND METHODS: The cells were treated with melatonin, IL-25 and IL-17B silencing gene and performed cell viability, gene and protein expression of caspase-3 and VEGFA (Vascular endothelial growth factor A) and an apoptosis membrane protein array. RESULTS: Treatment with 1 mM of melatonin reduced cell viability of both tumor cell lines, all treatments alone and combined significantly increased caspase-3 cleaved and proteins involved in the apoptotic pathway and reduced pro-angiogenic VEGFA, confirming the effectiveness of these potential promising treatments. CONCLUSION: This is the first study evaluating the potential use of these strategies in CF-41 and CMT-U229 cell lines and together encourages subsequent in vitro and in vivo studies for further exploration of clinical applications.


Assuntos
Apoptose/efeitos dos fármacos , Doenças do Cão/tratamento farmacológico , Interleucina-17/farmacologia , Neoplasias Mamárias Animais/tratamento farmacológico , Melatonina/farmacologia , Animais , Caspase 3/metabolismo , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Doenças do Cão/patologia , Cães , Feminino , Imunofluorescência/veterinária , Inativação Gênica , Neoplasias Mamárias Animais/patologia , Fator A de Crescimento do Endotélio Vascular/metabolismo
11.
G Chir ; 37(5): 206-210, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28098056

RESUMO

AIM: To evaluate the role of 320-detector row computed tomography (MDCT) with 3D analysis software in follow up of patients affected by multicentric hepatocellular carcinoma (HCC) treated with systemic therapy by using modified response evaluation criteria in solid tumors (mRECIST). PATIENTS AND METHODS: 38 patients affected by multicentric HCC underwent MDCT. All exams were performed before and after iodinate contrast material intravenous injection by using a 320-detection row CT device. CT images were analyzed by two radiologists using multi-planar reconstructions (MPR) in order to assess the response to systemic therapy according to mRECIST criteria: complete response (CR), partial response (PR), progressive disease (PD), stable disease (SD). 30 days later, the same two radiologists evaluated target lesion response to systemic therapy according to mRECIST criteria by using 3D analysis software. The difference between the two systems in assessing HCC response to therapy was assessed by the analysis of the variance (Anova Test). Interobserver agreement between the two radiologists by using MPR images and 3D analysis software was calculated by using Cohen's Kappa test. RESULTS: PR occurred in 10/38 cases (26%), PD in 6/38 (16%), SD in 22/38 (58%). Anova Test showed no statistically significant difference between the two systems for assessing target lesion response to therapy (p >0.05). Inter-observer agreement (k) was respectively of 0.62 for MPR images measurements and 0.86 for 3D analysis ones. CONCLUSIONS: 3D Analysis software provides a semiautomatic system for assessing target lesion response to therapy according to mRECIST criteria in patient affected by multifocal HCC treated with systemic therapy. The reliability of 3D analysis software makes it useful in the clinical practice.


Assuntos
Carcinoma Hepatocelular/diagnóstico por imagem , Carcinoma Hepatocelular/terapia , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/terapia , Tomografia Computadorizada Multidetectores/métodos , Critérios de Avaliação de Resposta em Tumores Sólidos , Idoso , Carcinoma Hepatocelular/diagnóstico , Progressão da Doença , Seguimentos , Humanos , Neoplasias Hepáticas/diagnóstico , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Valor Preditivo dos Testes , Estudos Retrospectivos , Sensibilidade e Especificidade , Tomografia Computadorizada por Raios X/métodos
12.
Leukemia ; 31(4): 853-860, 2017 04.
Artigo em Inglês | MEDLINE | ID: mdl-27773931

RESUMO

MYC is a major oncogenic driver of multiple myeloma (MM) and yet almost no therapeutic agents exist that target MYC in MM. Here we report that the let-7 biogenesis inhibitor LIN28B correlates with MYC expression in MM and is associated with adverse outcome. We also demonstrate that the LIN28B/let-7 axis modulates the expression of MYC, itself a let-7 target. Further, perturbation of the axis regulates the proliferation of MM cells in vivo in a xenograft tumor model. RNA-sequencing and gene set enrichment analyses of CRISPR-engineered cells further suggest that the LIN28/let-7 axis regulates MYC and cell cycle pathways in MM. We provide proof of principle for therapeutic regulation of MYC through let-7 with an LNA-GapmeR (locked nucleic acid-GapmeR) containing a let-7b mimic in vivo, demonstrating that high levels of let-7 expression repress tumor growth by regulating MYC expression. These findings reveal a novel mechanism of therapeutic targeting of MYC through the LIN28B/let-7 axis in MM that may impact other MYC-dependent cancers as well.


Assuntos
Regulação Neoplásica da Expressão Gênica , MicroRNAs/genética , Mieloma Múltiplo/genética , Interferência de RNA , Proteínas de Ligação a RNA/genética , Animais , Estudos de Casos e Controles , Ciclo Celular/genética , Linhagem Celular Tumoral , Análise por Conglomerados , Modelos Animais de Doenças , Perfilação da Expressão Gênica , Genes myc , Xenoenxertos , Humanos , Camundongos , Mieloma Múltiplo/tratamento farmacológico , Mieloma Múltiplo/mortalidade , Mieloma Múltiplo/patologia , Prognóstico , Proteínas de Ligação a RNA/metabolismo
13.
G Chir ; 37(3): 118-122, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27734795

RESUMO

AIM: To assess the role of breast US in diagnosing and classifying gynecomastia as the primary imaging modality and to compare US findings and classification system with the mammographic ones. PATIENTS AND METHODS: 48 patients suspected of having gynecomastia underwent mammography and US. Two radiologists in consensus retrospectively evaluated mammograms and sonograms. Both US and mammographic images were evaluated categorizing gynecomastia into non-mass, nodular and flame shaped patterns. The two category assignations were compared in order to find any difference. The reference standard for both the classification systems was represented by the cytological examination in 18 out of 44 cases (41%) and the six-month US follow-up in the remaining cases. RESULTS: The US examination revealed pseudo-gynecomastia in 4/48 (8%) and true gynecomastia in the remaining 44 (92%). Gynecomastia was bilateral in 25/44 cases (57%) and unilateral in the remaining 19 (43%). The cases of true gynecomastia included non mass shape in 26/44 cases (59%), nodular shape in 12 (27%) and flame shape in 6 (14%). The mammographic examination revealed the same results as compared with US findings. 18/44 (41%) patients affected by nodular or dendritic gynecomastia underwent cytological examination confirming the presence of glandular tissue and the benign nature of the clinical condition. CONCLUSIONS: US could be proposed as the primary imaging tool for diagnosing and classifying gynecomastia, avoiding unnecessary Xray examinations or invasive procedures in case of diffuse gynecomastia. In case of nodular or dendritic patterns, biopsy remains mandatory for a definitive diagnosis.


Assuntos
Ginecomastia/diagnóstico por imagem , Mamografia , Ultrassonografia , Adulto , Idoso , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Adulto Jovem
14.
Ann Oncol ; 27(8): 1449-55, 2016 08.
Artigo em Inglês | MEDLINE | ID: mdl-27037296

RESUMO

The significant activity of poly(ADP-ribose)polymerase (PARP) inhibitors in the treatment of germline BRCA mutation-associated ovarian cancer, which represents ∼15% of HGS cases, has recently led to European Medicines Agency and food and drug administration approval of olaparib. Accumulating evidence suggests that PARP inhibitors may have a wider application in the treatment of sporadic ovarian cancers. Up to 50% of HGS ovarian cancer patients may exhibit homologous recombination deficiency (HRD) through mechanisms including germline BRCA mutations, somatic BRCA mutations, and BRCA promoter methylation. In this review, we discuss the role of somatic BRCA mutations and BRCA methylation in ovarian cancer. There is accumulating evidence for routine somatic BRCA mutation testing, but the relevance of BRCA epigenetic modifications is less clear. We explore the challenges that need to be addressed if the full potential of these markers of HRD is to be utilised in clinical practice.


Assuntos
Proteína BRCA1/genética , Proteína BRCA2/genética , Cistadenocarcinoma Seroso/tratamento farmacológico , Neoplasias Ovarianas/tratamento farmacológico , Cistadenocarcinoma Seroso/genética , Cistadenocarcinoma Seroso/patologia , Metilação de DNA/efeitos dos fármacos , Feminino , Mutação em Linhagem Germinativa/genética , Recombinação Homóloga/efeitos dos fármacos , Humanos , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/patologia , Inibidores de Poli(ADP-Ribose) Polimerases/uso terapêutico
15.
Diagn Interv Imaging ; 97(3): 315-20, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26970658

RESUMO

OBJECTIVE: To investigate whether background parenchymal enhancement (BPE) may influence the sensitivity of dynamic contrast-enhanced magnetic resonance (DCE-MR) imaging in breast cancer detection. MATERIALS AND METHODS: A total of 180 consecutive women with 194 breast cancers underwent MR imaging examination. Women were assigned to two different groups depending on the degree of BPE. Group 1 consisted of women with minimal or mild BPE and group 2 of women with moderate or marked BPE. The distributions of histotypes of tumors within the two groups were compared using the χ(2) test. Difference in sensitivities of DCE-MR imaging for tumor detection between the two groups was searched for using the Student t-test. RESULTS: No differences in terms of distributions of histotypes of tumors between the two groups of women were found (P=0.5). The 11% difference in sensitivity of DCE-MR imaging for tumor detection between group 1 (91/92; 99%; 95% CI: 94-100%) and group 2 (90/102; 88%; 95% CI: 80-94%) was statistically significant (P=0.0058). CONCLUSION: The sensitivity of DCE-MR imaging is significantly lower in women with moderate and marked BPE as compared with women with minimal and mild BPE regardless of cancer histotype. BPE could represent a limitation for breast MR imaging interpretation and should be indicated in MR imaging reports.


Assuntos
Neoplasias da Mama/diagnóstico por imagem , Aumento da Imagem/métodos , Imageamento por Ressonância Magnética/métodos , Tecido Parenquimatoso/diagnóstico por imagem , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Pessoa de Meia-Idade , Estudos Retrospectivos , Sensibilidade e Especificidade
17.
Leukemia ; 30(5): 1103-15, 2016 05.
Artigo em Inglês | MEDLINE | ID: mdl-26859080

RESUMO

The role of endothelial progenitor cell (EPC)-mediated vasculogenesis in hematological malignancies is not well explored. Here, we showed that EPCs are mobilized from the bone marrow (BM) to the peripheral blood at early stages of multiple myeloma (MM); and recruited to MM cell-colonized BM niches. Using EPC-defective ID1+/- ID3-/- mice, we found that MM tumor progression is dependent on EPC trafficking. By performing RNA-sequencing studies, we confirmed that endothelial cells can enhance proliferation and favor cell-cycle progression only in MM clones that are smoldering-like and have dependency on endothelial cells for tumor growth. We further confirmed that angiogenic dependency occurs early and not late during tumor progression in MM. By using a VEGFR2 antibody with anti-vasculogenic activity, we demonstrated that early targeting of EPCs delays tumor progression, while using the same agent at late stages of tumor progression is ineffective. Thus, although there is significant angiogenesis in myeloma, the dependency of the tumor cells on EPCs and vasculogenesis may actually precede this step. Manipulating vasculogenesis at an early stage of disease may be examined in clinical trials in patients with smoldering MM, and other hematological malignancies with precursor conditions.


Assuntos
Mieloma Múltiplo/patologia , Neovascularização Patológica/tratamento farmacológico , Animais , Anticorpos/uso terapêutico , Medula Óssea , Movimento Celular , Células Clonais/patologia , Progressão da Doença , Células Endoteliais/patologia , Camundongos , Mieloma Múltiplo/irrigação sanguínea , Mieloma Múltiplo/tratamento farmacológico , Neovascularização Patológica/prevenção & controle , Prevenção Secundária , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/imunologia
18.
G Chir ; 36(5): 201-4, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26712255

RESUMO

AIM: To assess the diagnostic accuracy of specimen ultrasound (US) for predicting resection margin status in women undergoing breast conserving therapy for US-detected cancer, having the histological findings as the reference standard. PATIENTS AND METHODS: A total of 132 consecutive patients (age range, 34-87 years; mean, 51 years) underwent breast-conserving surgery for US-detected invasive breast cancer. All surgical specimens underwent US examination. The presence of lesion within the specimen and its distance from the specimen margins were assessed considering a threshold distance between the lesion and specimen margins of 10 mm. US findings were then compared with the pathological ones and specimen US. Sensitivity, specificity, diagnostic accuracy, positive (PPV) and negative predictive values (NPV) for predicting histological margin status were evaluated, having the histological findings as the reference standard. RESULTS: The histological examination detected invasive ductal carcinoma in 96/132 (73%) cases, invasive lobular carcinoma in 32/132 (24%), mucinous carcinoma in 4/132 (3%). The pathological margin analysis revealed 96/132 (73%) negative margins and 36 (27%) close/positive margins. US examination detected all 132 breast lesions within the surgical specimens. 110 (83%) negative margins and 22 (17%) positive margins were found on US. Sensitivity, specificity, diagnostic accuracy, PPV and NPV of 44%, 94%, 80%, 73% and 82%, respectively, were found for specimen US. CONCLUSIONS: Specimen US represents a time and cost saving imaging tool for evaluating the presence of US detected-breast lesion within surgical specimen and for predicting the histological margin status.


Assuntos
Adenocarcinoma Mucinoso/diagnóstico por imagem , Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/cirurgia , Carcinoma Ductal de Mama/diagnóstico por imagem , Carcinoma Lobular/diagnóstico por imagem , Mastectomia Segmentar , Adenocarcinoma Mucinoso/epidemiologia , Adenocarcinoma Mucinoso/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama/epidemiologia , Carcinoma Ductal de Mama/epidemiologia , Carcinoma Ductal de Mama/cirurgia , Carcinoma Lobular/epidemiologia , Carcinoma Lobular/cirurgia , Feminino , Humanos , Itália/epidemiologia , Mastectomia Segmentar/métodos , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Sensibilidade e Especificidade , Resultado do Tratamento , Ultrassonografia
19.
Clin Radiol ; 70(9): 948-53, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-26050069

RESUMO

AIM: To evaluate the effect of post-mastectomy radiation therapy (RT) on breast implants as detected by magnetic resonance imaging (MRI) searching for short-term complications. MATERIALS AND METHODS: One hundred and forty patients (total of 144 implants) were evaluated by MRI; 80 (group 1) had undergone RT, whereas the remaining 60 patients (group 2) underwent mastectomy with implant reconstruction without RT. Two radiologists evaluated MRI images searching for implant rupture signs, sub-capsular seromas, capsular contracture, soft-tissue oedema, peri-implant fluid collections. Implant ruptures were classified as severe complications; seromas and capsular contractures as moderate complications; oedema and fluid collections as mild complications. The prevalence of MRI findings in the two groups was calculated and compared by unpaired t-test. Cohen's kappa statistics was used to assess interobserver agreement. RESULTS: Sixty-nine out of 144 (48%) implants presented pathological findings at MRI with complication rates of 47.5 and 48.4 for groups 1 and 2, respectively. Two (5%) severe complications, 10 (26%) moderate complications, and 26 (69%) mild complications occurred in group 1 and surgical treatment was performed in 10 cases. Two (6%) severe complications, seven (23%) moderate complications, and 22 (71%) mild complications occurred in group 2 and surgical treatment was performed in eight cases. No significant difference between the two groups was found (p>0.1). Almost perfect agreement between the two radiologists was found for MRI image detection (k=0.86). CONCLUSION: RT does not seem to cause a significant effect on breast implants in terms of complication rate in patients undergoing implant-based breast reconstruction. One-stage immediate implant-based breast reconstruction performed at the same time as mastectomy could be proposed.


Assuntos
Implantes de Mama , Neoplasias da Mama/radioterapia , Neoplasias da Mama/cirurgia , Imageamento por Ressonância Magnética/métodos , Complicações Pós-Operatórias/diagnóstico , Adulto , Idoso , Terapia Combinada , Meios de Contraste , Feminino , Humanos , Mastectomia , Meglumina/análogos & derivados , Pessoa de Meia-Idade , Compostos Organometálicos , Prevalência , Estudos Prospectivos
20.
G Chir ; 35(7-8): 171-6, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25174291

RESUMO

AIM: To compare the diagnostic accuracy of fine-needle aspiration cytology (FNAC) and core needle biopsy (CNB) in patients with USdetected breast lesions. PATIENTS AND METHODS: Between September 2011 and May 2013, 3469 consecutive breast US examinations were performed. 400 breast nodules were detected in 398 patients. 210 FNACs and 190 CNBs were performed. 183 out of 400 (46%) lesions were surgically removed within 30 days form diagnosis; in the remaining cases, a six month follow up US examination was performed. Sensitivity, specificity, diagnostic accuracy, positive predictive (PPV) and negative predictive (NPV) values were calculated for FNAC and CNB. RESULTS: 174 out of 400 (43%) malignant lesions were found while the remaining 226 resulted to be benign lesions. 166 out of 210 (79%) FNACs and 154 out of 190 (81%) CNBs provided diagnostic specimens. Sensitivity, specificity, diagnostic accuracy, PPV and NPV of 97%, 94%, 95%, 91% and 98% were found for FNAC, and values of 92%, 82%, 89%, 92% and 82% were obtained for CNB. Sensitivity, specificity, diagnostic accuracy, PPV and NPV of 97%, 96%, 96%, 97% and 96% were found for FNAC, and values of 97%, 96%, 96%, 97% and 96% were obtained for CNB. CONCLUSION: FNAC and CNB provide similar values of diagnostic accuracy.


Assuntos
Biópsia por Agulha Fina , Biópsia com Agulha de Grande Calibre , Doenças Mamárias/patologia , Neoplasias da Mama/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Reprodutibilidade dos Testes , Adulto Jovem
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