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1.
Isr Med Assoc J ; 24(2): 85-88, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-35187896

RESUMO

BACKGROUND: Accuracy of the number and location of pathological lymph nodes (LNs) in the pathology report of a neck dissection (ND) is of vital importance. OBJECTIVES: To quantify the error rate in reporting the location and number of pathologic LNs in ND specimens. METHODS: All patients who had undergone a formal ND that included at least neck level 1 for a clinical N1 disease between January 2010 and December 2017 were included in the study. The error rate of the pathology reports was determined by various means: comparing preoperative imaging and pathological report, reporting a disproportionate LN distribution between the different neck levels, and determining an erroneous location of the submandibular gland (SMG) in the pathology report. Since the SMG must be anatomically located in neck level 1, any mistake in reporting it was considered a categorical error. RESULTS: A total of 227 NDs met the inclusion criteria and were included in the study. The study included 128 patients who had undergone a dissection at levels 1-3, 68 at levels 1-4, and 31 at levels 1-5. The best Kappa score for correlation between preoperative imaging and final pathology was 0.50. There were nine cases (3.9%) of a disproportionate LN distribution in the various levels. The SMG was inaccurately reported outside neck level 1 in 17 cases (7.5%). CONCLUSIONS: At least 7.5% of ND reports were inaccurate in this investigation. The treating physician should be alert to red flags in the pathological report.


Assuntos
Linfonodos/patologia , Metástase Linfática/diagnóstico , Erros Médicos/estatística & dados numéricos , Patologia Clínica/normas , Humanos , Metástase Linfática/patologia , Esvaziamento Cervical , Estudos Retrospectivos
2.
Int J Gynecol Cancer ; 23(4): 730-4, 2013 May.
Artigo em Inglês | MEDLINE | ID: mdl-23446379

RESUMO

OBJECTIVES: Israel is traditionally considered to have the lowest prevalence of cervical cancer compared with that in other countries of the Western world. The aim of the present study was to establish the human papillomavirus (HPV) genotypes distribution among Israeli Jewish women with premalignant and cervical cancer. METHODS: Fifty-two specimens with invasive cervical cancer and 50 specimens with high-grade cervical intraepithelial neoplasia (CIN2/3) were identified. Human papillomavirus genotyping in paraffin-embedded specimens was performed by deparaffinization of the tissue sections and DNA extraction, followed by HPV genotype detection using a validated polymerase chain reaction (PCR)-based HPV GenoArray test kit, to simultaneously identify 21 HPV genotypes. RESULTS: Forty-eight (48/52; 92.3%) cervical cancer samples demonstrated PCR-amplifiable DNA (non-HPV DNA). Forty (83.3%) of 48 samples were high-risk (HR) HPV positive. Six (12.5%) of 48 patients showed multiple HR HPV infections. Human papillomavirus types 16 and 18 dominated covering 28 (58.3%) and 14 (29.16%) of 48 samples. Human papillomavirus types 16 and 18 coinfected all 6 cases of multiple HR HPV infections. In CIN2/3 samples, 37 (78.7%) of 47 samples demonstrated PCR-amplifiable DNA (non-HPV DNA), and 20 (54.0%) of these 37 samples were infected by HPV. Human papillomavirus type 16 was found in 19 (95.0%) of 20 cases. Human papillomavirus type 18 was found in 3 (15.0%) of 20 cases; hence, HPV16 and HPV18 contributed to 100% of the cases. CONCLUSIONS: Human papillomavirus types 16 and 18 were responsible for the vast majority of invasive cervical cancer and CIN2/3 specimens (81.2% and 100%, respectively). Therefore, it is essential to include the HPV vaccine in the vaccine schedule of the Israeli population.


Assuntos
Carcinoma de Células Escamosas/virologia , Papillomavirus Humano 16/isolamento & purificação , Papillomavirus Humano 18/isolamento & purificação , Displasia do Colo do Útero/virologia , Neoplasias do Colo do Útero/virologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células Escamosas/genética , Criança , Feminino , Genótipo , Papillomavirus Humano 16/genética , Papillomavirus Humano 18/genética , Humanos , Israel , Pessoa de Meia-Idade , Estudos Retrospectivos , Neoplasias do Colo do Útero/genética , Adulto Jovem , Displasia do Colo do Útero/genética
3.
Biomolecules ; 13(9)2023 09 20.
Artigo em Inglês | MEDLINE | ID: mdl-37759818

RESUMO

Circulating tumor DNA (ctDNA) has been suggested as a surrogate biomarker for early detection of cancer recurrence. We aimed to explore the utility of ctDNA as a noninvasive prognostic biomarker in newly diagnosed head and neck squamous cell carcinoma (HNSCC) patients. Seventy HNSCC specimens were analysed for the detection of TP53 genetic alterations utilizing next-generation sequencing (NGS). TP53 mutations were revealed in 55 (79%). Upon detection of a significant TP53 mutation, circulating cell-free DNA was scrutinized for the presence of the tumor-specific mutation. ctDNA was identified at a minimal allele frequency of 0.08% in 21 out of 30 processed plasma samples. Detectable ctDNA correlated with regional spread (N stage ≥ 1, p = 0.011) and poorer 5-year progression-free survival (20%, 95% CI 10.9 to 28.9, p = 0.034). The high-risk worst pattern of invasion (WPOI grade 4-5) and deep invasion were frequently found in patients whose ctDNA was detected (p = 0.087 and p = 0.072, respectively). Detecting mutated TP53 ctDNA was associated with poor progression-free survival and regional metastases, indicating its potential role as a prognostic biomarker. However, ctDNA detectability in early-stage disease and the mechanisms modulating its release into the bloodstream must be further elucidated.


Assuntos
Ácidos Nucleicos Livres , DNA Tumoral Circulante , Neoplasias de Cabeça e Pescoço , Humanos , DNA Tumoral Circulante/genética , Carcinoma de Células Escamosas de Cabeça e Pescoço/genética , Biomarcadores , Neoplasias de Cabeça e Pescoço/diagnóstico , Neoplasias de Cabeça e Pescoço/genética , Proteína Supressora de Tumor p53/genética
4.
BMC Cancer ; 11: 130, 2011 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-21486440

RESUMO

BACKGROUND: The inflammatory chemokines CCL2 (MCP-1) & CCL5 (RANTES) and the inflammatory cytokines TNFα & IL-1ß were shown to contribute to breast cancer development and metastasis. In this study, we wished to determine whether there are associations between these factors along stages of breast cancer progression, and to identify the possible implications of these factors to disease course. METHODS: The expression of CCL2, CCL5, TNFα and IL-1ß was determined by immunohistochemistry in patients diagnosed with: (1) Benign breast disorders (=healthy individuals); (2) Ductal Carcinoma In Situ (DCIS); (3) Invasive Ducal Carcinoma without relapse (IDC-no-relapse); (4) IDC-with-relapse. Based on the results obtained, breast tumor cells were stimulated by the inflammatory cytokines, and epithelial-to-mesenchymal transition (EMT) was determined by flow cytometry, confocal analyses and adhesion, migration and invasion experiments. RESULTS: CCL2, CCL5, TNFα and IL-1ß were expressed at very low incidence in normal breast epithelial cells, but their incidence was significantly elevated in tumor cells of the three groups of cancer patients. Significant associations were found between CCL2 & CCL5 and TNFα & IL-1ß in the tumor cells in DCIS and IDC-no-relapse patients. In the IDC-with-relapse group, the expression of CCL2 & CCL5 was accompanied by further elevated incidence of TNFα & IL-1ß expression. These results suggest progression-related roles for TNFα and IL-1ß in breast cancer, as indeed indicated by the following: (1) Tumors of the IDC-with-relapse group had significantly higher persistence of TNFα and IL-1ß compared to tumors of DCIS or IDC-no-relapse; (2) Continuous stimulation of the tumor cells by TNFα (and to some extent IL-1ß) has led to EMT in the tumor cells; (3) Combined analyses with relevant clinical parameters suggested that IL-1ß acts jointly with other pro-malignancy factors to promote disease relapse. CONCLUSIONS: Our findings suggest that the coordinated expression of CCL2 & CCL5 and TNFα & IL-1ß may be important for disease course, and that TNFα & IL-1ß may promote disease relapse. Further in vitro and in vivo studies are needed for determination of the joint powers of the four factors in breast cancer, as well as analyses of their combined targeting in breast cancer.


Assuntos
Neoplasias da Mama/metabolismo , Carcinoma Ductal de Mama/metabolismo , Carcinoma Intraductal não Infiltrante/metabolismo , Mediadores da Inflamação/metabolismo , Adulto , Neoplasias da Mama/patologia , Neoplasias da Mama/terapia , Carcinoma Ductal de Mama/patologia , Carcinoma Intraductal não Infiltrante/patologia , Adesão Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Quimiocina CCL2/metabolismo , Quimiocina CCL5/metabolismo , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Feminino , Citometria de Fluxo , Humanos , Imuno-Histoquímica , Mediadores da Inflamação/farmacologia , Interleucina-1beta/farmacologia , Microscopia Confocal , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Fator de Necrose Tumoral alfa/farmacologia
5.
Laryngoscope ; 131(5): E1514-E1518, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33016337

RESUMO

OBJECTIVES/HYPOTHESIS: The effects of different electrocautery power settings on mucosal contraction and margin status in the oral cavity have not been well established. The aim of this study was to examine how different levels of electrocautery energy outputs affect oral mucosal tissue margins. STUDY DESIGN: Animal model. METHODS: A model of 23 adult rats was used (two specimens per rat). After anesthetizing the animals, a 6-mm biopsy punch marked the resection margin on the buccal mucosa (one per cheek). The specimens were excised by means of three energy levels, a cold knife, and monopolar diathermy that was set on either 20 W or 30 W cut modes. The specimens were evaluated for extent of contraction. RESULTS: A total of 45 samples were obtained and measured, including 15 specimens in the cold-knife group, 15 specimens in the 20 W group, and 15 specimens in the 30 W group. The median diameters of the specimens after resection were 4.5 mm for the cold-knife group (interquartile range [IQR] = 4.0-5.0), 3.5 mm for the 20 W group (IQR = 3.5-4.0), and 2.8 mm for the 30 W group (IQR = 2.5-3.0). Specimen contraction was 25.0%, 41.7%, and 53.3%, respectively. The difference in shrinkage between each pair was statistically significant: cold knife versus 20 W, P = .001; cold knife versus 30 W, P < .0001; and 20 W versus 30 W, P < .001. CONCLUSIONS: Diathermy power settings result in a significant difference of mucosal tissue contraction, with higher outputs resulting in a narrower mucosal margin. It is imperative that the surgical team take into consideration the diathermy settings during initial resection planning. Laryngoscope, 131:E1514-E1518, 2021.


Assuntos
Diatermia/métodos , Eletrocoagulação/métodos , Margens de Excisão , Mucosa Bucal/cirurgia , Neoplasias Bucais/cirurgia , Animais , Biópsia , Bochecha , Diatermia/efeitos adversos , Diatermia/instrumentação , Eletrocoagulação/efeitos adversos , Eletrocoagulação/instrumentação , Humanos , Modelos Animais , Mucosa Bucal/patologia , Ratos
6.
PLoS Med ; 6(2): e1000029, 2009 Feb 17.
Artigo em Inglês | MEDLINE | ID: mdl-19226183

RESUMO

BACKGROUND: Neural stem cells are currently being investigated as potential therapies for neurodegenerative diseases, stroke, and trauma. However, concerns have been raised over the safety of this experimental therapeutic approach, including, for example, whether there is the potential for tumors to develop from transplanted stem cells. METHODS AND FINDINGS: A boy with ataxia telangiectasia (AT) was treated with intracerebellar and intrathecal injection of human fetal neural stem cells. Four years after the first treatment he was diagnosed with a multifocal brain tumor. The biopsied tumor was diagnosed as a glioneuronal neoplasm. We compared the tumor cells and the patient's peripheral blood cells by fluorescent in situ hybridization using X and Y chromosome probes, by PCR for the amelogenin gene X- and Y-specific alleles, by MassArray for the ATM patient specific mutation and for several SNPs, by PCR for polymorphic microsatellites, and by human leukocyte antigen (HLA) typing. Molecular and cytogenetic studies showed that the tumor was of nonhost origin suggesting it was derived from the transplanted neural stem cells. Microsatellite and HLA analysis demonstrated that the tumor is derived from at least two donors. CONCLUSIONS: This is the first report of a human brain tumor complicating neural stem cell therapy. The findings here suggest that neuronal stem/progenitor cells may be involved in gliomagenesis and provide the first example of a donor-derived brain tumor. Further work is urgently needed to assess the safety of these therapies.


Assuntos
Ataxia Telangiectasia/cirurgia , Neoplasias Encefálicas/etiologia , Neoplasias Encefálicas/patologia , Neurônios/patologia , Neurônios/transplante , Transplante de Células-Tronco/efeitos adversos , Células-Tronco/patologia , Adolescente , Neoplasias Encefálicas/diagnóstico , Humanos , Doadores Vivos , Masculino
7.
Eur J Surg Oncol ; 45(7): 1182-1187, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30928335

RESUMO

OBJECTIVE: We aimed to determine the frequency and risk of malignancy (ROM) for indeterminate thyroid nodules, categories III (B3) and IV (B4) of the Bethesda System for Reporting Thyroid Cytopathology (BSRTC), at a large institution in Israel. Additionally, we investigated the impact of redefining follicular neoplasm with papillary-like nuclear features (NIFTP) as non-malignant on malignancy rates. METHODS: In this retrospective study of all thyroid fine needle aspirations (FNAs) performed at Tel Aviv-Sourasky Medical Center between January 2013 and December 2015, we assessed ROM for B3 and B4 nodules. Potential risk factors thought to affect a-priori ROM were assessed. Suspected NIFTP lesions were re-examined, and if proven, reclassified as benign. RESULTS: 3701 nodules were sampled in 2919 FNAs performed on 2674 patients. B3 reports comprised 7.7% of all nodules (n = 284); B4 represented 3.6% (n = 132). In multivariate logistic regression, male gender, being of former Soviet Union origin, and smoking increased ROM for B3 nodules by a factor of 7.97 (P = 0.002; CI: 2.2-23.4), 9.15 (P = 0.021; CI:1.4-60.0), and 11.0 (P = 0.001; CI 2.8-44.8), respectively. Reclassifying NIFTP decreased ROM from 14% to 12.5% for B3, and from 26.7% to 25% for B4 nodules. NIFTP comprised 9.5% of previously diagnosed resected malignant tumors. CONCLUSIONS: The relative frequencies of B3 and B4 nodules and their associated malignancy rates were consistent with previous series. Risk factors identified for malignancy may help characterize patients most likely to benefit from surgery. Reclassifying NIFTP had a substantial impact on the ROM in the resected tumors previously diagnosed as malignant.


Assuntos
Adenocarcinoma Folicular/patologia , Adenoma/patologia , Neoplasias da Glândula Tireoide/patologia , Nódulo da Glândula Tireoide/patologia , Adenocarcinoma Folicular/epidemiologia , Adulto , Idoso , Biópsia por Agulha Fina , Feminino , Humanos , Israel/epidemiologia , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Estadiamento de Neoplasias , Estudos Retrospectivos , Risco , Câncer Papilífero da Tireoide/epidemiologia , Neoplasias da Glândula Tireoide/epidemiologia
8.
Nat Commun ; 10(1): 4375, 2019 09 26.
Artigo em Inglês | MEDLINE | ID: mdl-31558756

RESUMO

Cancer-Associated Fibroblasts (CAFs) were shown to orchestrate tumour-promoting inflammation in multiple malignancies, including breast cancer. However, the molecular pathways that govern the inflammatory role of CAFs are poorly characterised. In this study we found that fibroblasts sense damage-associated molecular patterns (DAMPs), and in response activate the NLRP3 inflammasome pathway, resulting in instigation of pro-inflammatory signalling and secretion of IL-1ß. This upregulation was evident in CAFs in mouse and in human breast carcinomas. Moreover, CAF-derived inflammasome signalling facilitated tumour growth and metastasis, which was attenuated when NLRP3 or IL-1ß were specifically ablated. Functionally, CAF-derived inflammasome promoted tumour progression and metastasis by modulating the tumour microenvironment towards an immune suppressive milieu and by upregulating the expression of adhesion molecules on endothelial cells. Our findings elucidate a mechanism by which CAFs promote breast cancer progression and metastasis, by linking the physiological tissue damage response of fibroblasts with tumour-promoting inflammation.


Assuntos
Neoplasias da Mama/metabolismo , Fibroblastos Associados a Câncer/metabolismo , Inflamassomos/metabolismo , Inflamação/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Animais , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Linhagem Celular Tumoral , Progressão da Doença , Feminino , Humanos , Inflamassomos/genética , Inflamação/genética , Interleucina-1beta/metabolismo , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Camundongos Knockout , Camundongos Transgênicos , Proteína 3 que Contém Domínio de Pirina da Família NLR/genética , Metástase Neoplásica , Transdução de Sinais/genética , Microambiente Tumoral/genética
9.
Cytokine ; 44(1): 191-200, 2008 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-18790652

RESUMO

The chemokines RANTES (CCL5) and MCP-1 (CCL2) were suggested to contribute, independently, to breast malignancy. In the present study, we asked if the two chemokines are jointly expressed in clinical samples of breast cancer patients, and do they interact in breast tumor cells. We found that RANTES and MCP-1 were expressed by breast tumor cells in primary tumors of Ductal Carcinoma In Situ and of Invasive Ductal Carcinoma, but minimally in normal breast epithelial duct cells. The chemokines were also detected in metastases and pleural effusions. Novel findings showed that co-expression of RANTES and MCP-1 in the same tumor was associated with more advanced stages of disease, suggesting that breast tumors "benefit" from interactions between the two chemokines. Accordingly, MCP-1 significantly promoted the release of RANTES from endogenous pre-made vesicles, in an active process that depended on calcium from intracellular and extracellular sources, and on intracellular transport of RANTES towards exocytosis. Our findings show a chemokine-triggered release of stored pro-malignancy chemokine from breast tumor cells. These observations support a major tumor-promoting role for co-expression of the chemokines in breast malignancy, and agree with the significant association of joint RANTES and MCP-1 expression with advanced stages of breast cancer.


Assuntos
Neoplasias da Mama/metabolismo , Quimiocina CCL2/biossíntese , Quimiocina CCL5/biossíntese , Neoplasias da Mama/patologia , Carcinoma Ductal de Mama/metabolismo , Carcinoma Ductal de Mama/patologia , Carcinoma Intraductal não Infiltrante/metabolismo , Carcinoma Intraductal não Infiltrante/patologia , Linhagem Celular Tumoral , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Metástase Neoplásica/fisiopatologia , Derrame Pleural/metabolismo
10.
Pathol Res Pract ; 204(5): 323-8, 2008.
Artigo em Inglês | MEDLINE | ID: mdl-18304754

RESUMO

Quality assurance has become an integral part of surgical pathology. Despite the development of interdisciplinary quality systems, however, the means for objective analysis in surgical pathology are limited. Immunohistostaining is a multi-factorial procedure that depends on the quality of reagents and antibodies employed in the process and on technical methodology. In the present study, we aim to establish a straightforward procedure for objective quality evaluation of the components involved in immunohistostaining. The quality of two of these components, the primary antibody and the automated staining device, was assessed by employing each component from two different sources, one serving as the test substance and the second as the reference. Assessment was performed by at least two pathologists in a blinded fashion using pre-established quality criteria and scores. The quality analysis of two automated devices revealed a significant difference between the reference and tested devices (3.5+/-1.7 and 4.2+/-1.5, respectively, P>0.05), while the analysis of two selected antibodies did not reveal any statistical difference. The described method provided objective quality assessment of selected components affecting immunohistostaining by elaborating numeric values that enabled statistical analysis. This approach is applicable to any given component in various surgical pathology procedures.


Assuntos
Anticorpos , Imuno-Histoquímica/normas , Patologia Cirúrgica/normas , Especificidade de Anticorpos , Automação , Humanos , Imuno-Histoquímica/instrumentação , Variações Dependentes do Observador , Patologia Cirúrgica/instrumentação , Proteínas Proto-Oncogênicas c-kit/análise , Proteínas Proto-Oncogênicas c-kit/imunologia , Controle de Qualidade , Padrões de Referência , Reprodutibilidade dos Testes , Sinaptofisina/análise , Sinaptofisina/imunologia , Fator A de Crescimento do Endotélio Vascular/análise , Fator A de Crescimento do Endotélio Vascular/imunologia , Vimentina/análise , Vimentina/imunologia
11.
Ophthalmic Surg Lasers Imaging ; 39(2): 146-9, 2008.
Artigo em Inglês | MEDLINE | ID: mdl-18435341

RESUMO

Two patients evaluated for metamorphopsia were noted to have inferotemporal retinal pigment epithelium elevations formed by a yellowish lesion. Fluorescein angiography showed granular hyperfluorescence with late leakage, which was interpreted as an occult choroidal neovascularization. One patient underwent photodynamic therapy. In both patients, neither vitreous cells nor neurologic manifestations were evident on presentation. Subsequent neurological signs appeared that prompted performance of brain imaging, which confirmed a space-occupying lesion. In both patients, the tumor was proven on histopathologic examination of brain tissue to be central nervous system lymphoma. Awareness of other possible underlying pathologies is warranted in cases of atypical choroidal neovascularization.


Assuntos
Neoplasias Encefálicas/diagnóstico , Neovascularização de Coroide/diagnóstico , Linfoma de Células B/diagnóstico , Neoplasias Uveais/diagnóstico , Idoso , Biomarcadores Tumorais/análise , Neoplasias Encefálicas/química , Neoplasias Encefálicas/terapia , Diagnóstico Diferencial , Angiofluoresceinografia , Humanos , Linfoma de Células B/química , Linfoma de Células B/terapia , Masculino , Pessoa de Meia-Idade , Neoplasias Uveais/química , Neoplasias Uveais/terapia
12.
J Exp Med ; 215(12): 3075-3093, 2018 12 03.
Artigo em Inglês | MEDLINE | ID: mdl-30470719

RESUMO

Cancer-associated fibroblasts (CAFs) are highly prominent in breast tumors, but their functional heterogeneity and origin are still largely unresolved. We report that bone marrow (BM)-derived mesenchymal stromal cells (MSCs) are recruited to primary breast tumors and to lung metastases and differentiate to a distinct subpopulation of CAFs. We show that BM-derived CAFs are functionally important for tumor growth and enhance angiogenesis via up-regulation of Clusterin. Using newly generated transgenic mice and adoptive BM transplantations, we demonstrate that BM-derived fibroblasts are a substantial source of CAFs in the tumor microenvironment. Unlike resident CAFs, BM-derived CAFs do not express PDGFRα, and their recruitment resulted in a decrease in the percentage of PDGFRα-expressing CAFs. Strikingly, decrease in PDGFRα in breast cancer patients was associated with worse prognosis, suggesting that BM-derived CAFs may have deleterious effects on survival. Therefore, PDGFRα expression distinguishes two functionally unique CAF populations in breast tumors and metastases and may have important implications for patient stratification and precision therapeutics.


Assuntos
Células da Medula Óssea/metabolismo , Neoplasias da Mama/metabolismo , Neoplasias Mamárias Animais/metabolismo , Células-Tronco Mesenquimais/metabolismo , Proteínas de Neoplasias/metabolismo , Receptor alfa de Fator de Crescimento Derivado de Plaquetas/metabolismo , Microambiente Tumoral , Animais , Células da Medula Óssea/patologia , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Feminino , Fibroblastos , Humanos , Neoplasias Mamárias Animais/genética , Neoplasias Mamárias Animais/patologia , Células-Tronco Mesenquimais/patologia , Camundongos , Camundongos Transgênicos , Metástase Neoplásica , Proteínas de Neoplasias/genética , Receptor alfa de Fator de Crescimento Derivado de Plaquetas/genética
13.
Clin Cancer Res ; 12(15): 4474-80, 2006 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-16899591

RESUMO

PURPOSE: The aim of this study was to determine the prognostic value of the chemokine CCL5, considered as a promalignancy factor in breast cancer, in predicting breast cancer progression and to evaluate its ability to strengthen the prognostic significance of other biomarkers. EXPERIMENTAL DESIGN: The expression of CCL5, alone and in conjunction with estrogen receptor (ER)-alpha, ER-beta, progesterone receptor (PR), and HER-2/neu (ErbB2), was determined in breast tumor cells by immunohistochemistry. The study included 142 breast cancer patients, including individuals in whom disease has progressed. RESULTS: Using Cox proportional hazard models, univariate analysis suggested that, in stage I breast cancer patients, CCL5 was not a significant predictor of disease progression. In contrast, in stage II patients, the expression of CCL5 (CCL5(+)), the absence of ER-alpha (ER-alpha(-)), and the lack of PR expression (PR(-)) increased significantly the risk for disease progression (P = 0.0045, 0.0041, and 0.0107, respectively). The prognostic strength of CCL5, as well as of ER-alpha(-), improved by combining them together (CCL5(+)/ER-alpha(-): P = 0.0001), being highly evident in the stage IIA subgroup [CCL5(+)/ER-alpha(-) (P = 0.0003); ER-alpha(-) (P = 0.0315)]. In the stage II group as a whole, the combinations of CCL5(-)/ER-alpha(+) and CCL5(-)/PR(+) were highly correlated with an improved prognosis. Multivariate analysis indicated that, in stage II patients, ER-alpha and CCL5 were independent predictors of disease progression. CONCLUSIONS: CCL5 could be considered as a biomarker for disease progression in stage II breast cancer patients, with the CCL5(+)/ER-alpha(-) combination providing improved prediction of disease progression, primarily in the stage IIA subgroup.


Assuntos
Biomarcadores Tumorais/genética , Neoplasias da Mama/genética , Quimiocina CCL5/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama/diagnóstico , Progressão da Doença , Feminino , Humanos , Imuno-Histoquímica , Pessoa de Meia-Idade , Análise Multivariada , Estadiamento de Neoplasias , Valor Preditivo dos Testes , Prognóstico
14.
Skull Base ; 17(1): 25-37, 2007 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-17603642

RESUMO

OBJECTIVE: To present our method for anterior skull base reconstruction after oncological resections. METHODS: One hundred nine patients who had undergone 120 anterior skull base resections of tumors (52 malignant [43%], 68 benign [57%]) via the subcranial approach were studied. Limited dural defects were closed primarily or reconstructed using a temporalis fascia. Large anterior skull base defects were reconstructed by a double-layer fascia lata graft. A split calvarial bone graft, posterior frontal sinus wall, or three-dimensional titanium mesh were used when the tumor involved the frontal, nasal, or orbital bones. A temporalis muscle flap was used to cover the orbital socket for cases of eye globe exenteration, and a rectus abdominis free flap was used for subcranial-orbitomaxillary resection. Pericranial flap wrapping of the frontonaso-orbital segment was performed to prevent osteoradionecrosis if perioperative radiotherapy was planned. RESULTS: The incidence of cerebrospinal fluid (CSF) leak, intracranial infection, and tension pneumocephalus was 5%. Histopathological and immunohistochemical analysis of fascia lata grafts in reoperated patients (n = 7) revealed integration of vascularized fibrous tissue to the graft and local proliferation of a newly formed vascular layer embedding the fascial sheath. CONCLUSION: A double-layer fascial graft alone was adequate for preventing CSF leak, meningitis, tension pneumocephalus, and brain herniation. We describe a simple and effective method of anterior skull base reconstruction after resections of both malignant and benign tumors.

15.
Photomed Laser Surg ; 25(3): 137-43, 2007 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-17603852

RESUMO

OBJECTIVE: This pilot double-blind randomized study evaluated the efficacy of 780-nm laser phototherapy on the acceleration of axonal growth and regeneration after peripheral nerve reconstruction by polyglycolic acid (PGA) neurotube. BACKGROUND DATA: The use of a guiding tube for the reconstruction of segmental loss of injured peripheral nerve has some advantages over the regular nerve grafting procedure. Experimental studies have shown that laser phototherapy is effective in influencing nerve regeneration. METHODS: The right sciatic nerve was transected, and a 0.5-cm nerve segment was removed in 20 rats. A neurotube was placed between the proximal and the distal parts of the nerve for reconnection of nerve defect. Ten of 20 rats received post-operative, transcutaneous, 200-mW, 780-nm laser irradiation for 14 consecutive days to the corresponding segments of the spinal cord (15 min) and to the reconstructed nerve (15 min). RESULTS: At 3 months after surgery, positive somato-sensory evoked responses were found in 70% of the irradiated rats (p = 0.015), compared to 30% of the non-irradiated rats. The Sciatic Functional Index in the irradiated group was higher than in the non-irradiated group (p < 0.05). Morphologically, the nerves were completely reconnected in both groups, but the laser-treated group showed an increased total number of myelinated axons. CONCLUSION: The results of this study suggest that postoperative 780-nm laser phototherapy enhances the regenerative process of the peripheral nerve after reconnection of the nerve defect using a PGA neurotube.


Assuntos
Terapia com Luz de Baixa Intensidade , Regeneração Nervosa/efeitos da radiação , Nervos Periféricos/fisiologia , Animais , Método Duplo-Cego , Potenciais Somatossensoriais Evocados , Masculino , Projetos Piloto , Ácido Poliglicólico , Distribuição Aleatória , Ratos , Ratos Wistar , Nervo Isquiático/patologia
16.
Harefuah ; 146(2): 99-101, 166-7, 2007 Feb.
Artigo em Hebraico | MEDLINE | ID: mdl-17352276

RESUMO

The cat eye syndrome is a congenital malformation usually associated with anal atresia, ocular coloboma, downward slanting eyes, microphthalmia, hypertelorism, strabismus, preauricular tags or fistulas, congenital heart defect particularly septal defect, urinary tract abnormalities, skeletal anomalies and frequently mental and physical retardation. A small supernumerary chromosome (smaller than chromosome 21) is present, frequently has 2 centromeres, is bisatellited and represents an inv dup 22 (q11). A two years old female presented to our department with an association of cat eye syndrome with preauricular tags and a first branchial arch anomaly. This article discusses the surgical management and the association between the cat eye syndrome and first branchial cleft anomaly.


Assuntos
Região Branquial/anormalidades , Região Branquial/cirurgia , Coloboma/complicações , Coloboma/cirurgia , Centrômero/genética , Pré-Escolar , Feminino , Humanos
17.
J Clin Pathol ; 70(6): 500-507, 2017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-27798083

RESUMO

AIMS: The distinction between benign and malignant thyroid nodules has important therapeutic implications. Our objective was to develop an assay that could classify indeterminate thyroid nodules as benign or suspicious, using routinely prepared fine needle aspirate (FNA) cytology smears. METHODS: A training set of 375 FNA smears was used to develop the microRNA-based assay, which was validated using a blinded, multicentre, retrospective cohort of 201 smears. Final diagnosis of the validation samples was determined based on corresponding surgical specimens, reviewed by the contributing institute pathologist and two independent pathologists. Validation samples were from adult patients (≥18 years) with nodule size >0.5 cm, and a final diagnosis confirmed by at least one of the two blinded, independent pathologists. The developed assay, RosettaGX Reveal, differentiates benign from malignant thyroid nodules, using quantitative RT-PCR. RESULTS: Test performance on the 189 samples that passed quality control: negative predictive value: 91% (95% CI 84% to 96%); sensitivity: 85% (CI 74% to 93%); specificity: 72% (CI 63% to 79%). Performance for cases in which all three reviewing pathologists were in agreement regarding the final diagnosis (n=150): negative predictive value: 99% (CI 94% to 100%); sensitivity: 98% (CI 87% to 100%); specificity: 78% (CI 69% to 85%). CONCLUSIONS: A novel assay utilising microRNA expression in cytology smears was developed. The assay distinguishes benign from malignant thyroid nodules using a single FNA stained smear, and does not require fresh tissue or special collection and shipment conditions. This assay offers a valuable tool for the preoperative classification of thyroid samples with indeterminate cytology.


Assuntos
MicroRNAs/metabolismo , Neoplasias da Glândula Tireoide/diagnóstico , Nódulo da Glândula Tireoide/diagnóstico , Biópsia por Agulha Fina , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Variações Dependentes do Observador , Valor Preditivo dos Testes
18.
Clin Lymphoma Myeloma ; 6(5): 407-9, 2006 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-16640819

RESUMO

Rituximab, a chimeric anti-CD20 monoclonal antibody, is commonly being used to treat indolent and aggressive B-cell non-Hodgkin's lymphoma. Rituximab is considered a relatively safe drug, but recently, severe and fatal adverse effects related to this drug have been reported. In this regard, we report an 80-year-old patient with follicular grade 3 non-Hodgkin's lymphoma who developed a fatal interstitial pneumonitis related to treatment with a rituximab/CHOP (cyclophosphamide/doxorubicin/vincristine/prednisone) regimen. The pneumonitis was diagnosed on a routine midtreatment positron emission tomography/computed tomography scan when the patient was almost asymptomatic. Pulmonary deterioration occurred as the treatment with rituximab/CHOP was continued. In this article, we also review the literature on rituximab-associated pneumonitis, and we discuss the differential diagnosis with cyclophosphamide-induced lung injury.


Assuntos
Anticorpos Monoclonais/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Doenças Pulmonares Intersticiais/induzido quimicamente , Linfoma não Hodgkin/tratamento farmacológico , Idoso , Idoso de 80 Anos ou mais , Anticorpos Monoclonais/uso terapêutico , Anticorpos Monoclonais Murinos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Biópsia por Agulha , Ciclofosfamida/efeitos adversos , Ciclofosfamida/uso terapêutico , Progressão da Doença , Relação Dose-Resposta a Droga , Doxorrubicina/efeitos adversos , Doxorrubicina/uso terapêutico , Esquema de Medicação , Evolução Fatal , Humanos , Imuno-Histoquímica , Doenças Pulmonares Intersticiais/fisiopatologia , Linfoma não Hodgkin/patologia , Masculino , Estadiamento de Neoplasias , Prednisolona/efeitos adversos , Prednisolona/uso terapêutico , Radiografia Torácica , Medição de Risco , Rituximab , Tomografia Computadorizada por Raios X , Vincristina/efeitos adversos , Vincristina/uso terapêutico
19.
Laryngoscope ; 116(6): 1002-6, 2006 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-16735918

RESUMO

HYPOTHESIS/OBJECTIVES: We tested the effectiveness of a temperature-controlled CO2 laser soldering system on a porcine model for dural defect reconstruction using a fascial patch. METHODS: A dural patch was excised and then reconstructed with fascia by a CO2 laser system in vitro in 27 animals and in vivo in five animals. RESULTS: After dural reconstruction, the average burst pressure of the soldered patch in vitro, as measured by a custom-made pressure detector, was 258.5 cm H2O. All five pigs in the in vivo group showed no neurological complications or cerebrospinal fluid leak, and the underlying brain tissue showed no thermal injury. CONCLUSION: The CO2 laser system created a watertight bond and did not cause thermal injury to the brain. The procedure is potentially faster than conventional repair, and wound healing may also be more rapid.


Assuntos
Dura-Máter/cirurgia , Fasciotomia , Terapia a Laser , Animais , Modelos Animais de Doenças , Técnicas In Vitro , Terapia a Laser/instrumentação , Suínos
20.
Skull Base ; 16(4): 201-5, 2006 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-17471319

RESUMO

Necrotizing fasciitis is a rapidly progressing, life-threatening soft tissue bacterial infection found more frequently in immunocompromised subjects and rarely in the head and neck. We report a rare case of a patient with acquired immunodeficiency syndrome (AIDS) and non-Hodgkin's lymphoma (NHL) who presented with a high fever and supraorbital cellulitis 1 week after undergoing chemotherapy. He received intravenous antibiotic therapy but soon developed dyspnea and trismus with rapid extension of the cellulitis to the face, ipsilateral infratemporal fossa (ITF), and bilateral neck. An awake tracheotomy was followed by surgical exploration and drainage and debridement of the supraorbital and ITF areas, parotid gland, and bilateral neck. He received intravenous antibiotic therapy and the surgical wound was regularly debrided for 10 days. Following a gradual recovery, the patient was discharged 2 weeks later. Early antibiotic therapy, wide surgical exploration, and a secured airway are the therapeutic mainstay for necrotizing fasciitis of the skull base and neck.

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