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Am J Clin Pathol ; 153(2): 190-197, 2020 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-31618415


OBJECTIVES: In patients with lung cancer undergoing mediastinal staging through endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA), decisions are based on rapid on-site evaluation (ROSE) findings. We aimed to analyze the concordance rate between ROSE diagnosis and final diagnosis. METHODS: A prospective study was carried out in patients undergoing EBUS-TBNA for lung cancer staging. Diagnosis concordance was defined as cases where lymph nodes (LNs) presented the same diagnosis in ROSE and final diagnosis. Determinants of concordance were analyzed. RESULTS: Sixty-four patients were included and 637 LNs sampled. ROSE diagnosis was concordant with final diagnosis in 612 (96.1%) LNs and nonconcordant in 25 (3.9%). Differences in the concordance rate were found between pathologists, ROSE diagnoses, presence of cell block, number of passes, and number of slides. The staging status was changed between ROSE and the final diagnosis in three (4.6%) patients. CONCLUSIONS: ROSE diagnosis has a high concordance with the final diagnosis.

Am J Surg Pathol ; 41(7): 877-886, 2017 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-28288039


MYC translocation is a defining feature of Burkitt lymphoma (BL), and the new category of high-grade B-cell lymphomas with MYC and BCL2 and/or BCL6 translocations, and occurs in 6% to 15% of diffuse large B-cell lymphomas (DLBCLs). The low incidence of MYC translocations in DLBCL makes the genetic study of all these lymphomas cumbersome. Strategies based on an initial immunophenotypic screening to select cases with a high probability of carrying the translocation may be useful. LMO2 is a germinal center marker expressed in most lymphomas originated in these cells. Mining gene expression profiling studies, we observed LMO2 downregulation in BL and large B-cell lymphoma (LBCL) with MYC translocations, and postulated that LMO2 protein expression could assist to identify such cases. We analyzed LMO2 protein expression in 46 BLs and 284 LBCL. LMO2 was expressed in 1/46 (2%) BL cases, 146/268 (54.5%) DLBCL cases, and 2/16 (12.5%) high-grade B-cell lymphoma cases with MYC and BCL2 and/or BCL6 translocations. All BLs carried MYC translocation (P<0.001), whereas LMO2 was only positive in 6/42 (14%) LBCL with MYC translocation (P<0.001). The relationship between LMO2 negativity and MYC translocation was further analyzed in different subsets of tumors according to CD10 expression and cell of origin. Lack of LMO2 expression was associated with the detection of MYC translocations with high sensitivity (87%), specificity (87%), positive predictive value and negative predictive value (74% and 94%, respectively), and accuracy (87%) in CD10 LBCL. Comparing LMO2 and MYC protein expression, all statistic measures of performance of LMO2 surpassed MYC in CD10 LBCL. These findings suggest that LMO2 loss may be a good predictor for the presence of MYC translocation in CD10 LBCL.

Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Biomarcadores Tumorais/metabolismo , Linfoma de Burkitt/metabolismo , Genes myc , Proteínas com Domínio LIM/metabolismo , Linfoma Difuso de Grandes Células B/metabolismo , Proteínas Proto-Oncogênicas/metabolismo , Translocação Genética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Linfoma de Burkitt/genética , Linfoma de Burkitt/patologia , Criança , Pré-Escolar , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Imuno-Histoquímica , Linfoma Difuso de Grandes Células B/genética , Linfoma Difuso de Grandes Células B/patologia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Adulto Jovem
Int J Surg Case Rep ; 25: 153-5, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27372030


INTRODUCTION: The "open abdomen" expression widely used to define a full-thickness defect of the abdominal wall intentionally made in some situations like abdominal compartment syndrome, has been replaced by a newest one called "laparostomy". The definitive closure of an open abdomen with a giant full abdominal thickness defect remains a problem. CASE REPORT: We present a 67-year old male with a descompressive laparostomy treated with a greater omentum flap sutured hermetically with interrupted stitches at the edges of the muscle wall, reinforced with large mesh of polypropylene (PP) placed on-lay and sutured to the fascia by two concentric running sutures of polypropylene. A vacuum-assisted closure device was placed on the second postoperative day and it was kept during three weeks. By then the PP mesh was completely integrated so skin grafts were applied to the surface of the granulation tissue. An incisional hernia was easily repaired at three years of follow-up. Eight months after the last surgery the patient is satisfied with the result achieved. DISCUSSION: The great omentum has immunological and angiogenic properties that allow a rapid integration of the polypropylene mesh, even in septic environments, facilitating the engraftment of split-thickness skin graft. The reactive fibrosis caused by the PP mesh replaces the fat tissue but the inner surface is preserved, thereby avoiding subsequent adhesion and facilitates surgical access to the abdominal cavity if necessary in the future. CONCLUSION: The structure achieved is a strong structure, capable of visceral isolation that can be useful to close some OA.

Surgery ; 157(2): 249-59, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25616941


BACKGROUND: Ischemic preconditioning (IPC) and anesthetic preconditioning (APC) have been reported to attenuate ischemia-reperfusion (IR) injury after liver resection under continuous inflow occlusion. This study evaluates whether these strategies enhance hepatic protection of remnant liver against IR after liver resection with intermittent clamping (INT). METHODS: A total of 106 patients without underlying liver disease and submitted to liver resection using INT were randomized into 3 groups: IPC (10 minutes of inflow occlusion followed by 10 minutes of reperfusion before liver transection), APC (sevoflurane administration for 20 minutes before liver transection), and INT (no preconditioning). Patients were also stratified according to the extent of the hepatectomy. Cytoprotection was evaluated by comparing hepatocyte and endothelial dysfunction markers, apoptosis, histologic lesions, and postoperative outcome. RESULTS: No differences were observed in preoperative chemotherapy and steatosis, total warm ischemia time, operative time, or blood loss. Kinetics of transaminases (aspartate aminotransferase, P = .137; alanine aminotransferase, P = .616), bilirubin (P = .980), and hyaluronic acid increase (P = .514) revealed no differences. Significant apoptosis was present in 40% of patients, mild-to-moderate leukocyte infiltration and steatosis in 45% and 55%, respectively, and mild sinusoidal congestion in 65%, with a similar distribution in the 3 groups. When patients were stratified by major versus minor resections, no differences were observed in any of the variables studied. Postoperative clinical outcomes were also similar. CONCLUSION: These results suggest that these protocols of IPC and APC used in this study do not provide better cytoprotection from IR when INT is used.

Hepatectomia/métodos , Precondicionamento Isquêmico/métodos , Neoplasias Hepáticas/cirurgia , Traumatismo por Reperfusão/prevenção & controle , Adulto , Idoso , Idoso de 80 Anos ou mais , Anestésicos Inalatórios/administração & dosagem , Caspase 3/metabolismo , Feminino , Hepatectomia/efeitos adversos , Humanos , Fígado/irrigação sanguínea , Fígado/lesões , Fígado/fisiopatologia , Testes de Função Hepática , Masculino , Éteres Metílicos/administração & dosagem , Pessoa de Meia-Idade , Óxido Nítrico Sintase Tipo II/genética , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Sevoflurano
Proc Natl Acad Sci U S A ; 110(45): 18250-5, 2013 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-24145436


Mantle cell lymphoma (MCL) is an aggressive tumor, but a subset of patients may follow an indolent clinical course. To understand the mechanisms underlying this biological heterogeneity, we performed whole-genome and/or whole-exome sequencing on 29 MCL cases and their respective matched normal DNA, as well as 6 MCL cell lines. Recurrently mutated genes were investigated by targeted sequencing in an independent cohort of 172 MCL patients. We identified 25 significantly mutated genes, including known drivers such as ataxia-telangectasia mutated (ATM), cyclin D1 (CCND1), and the tumor suppressor TP53; mutated genes encoding the anti-apoptotic protein BIRC3 and Toll-like receptor 2 (TLR2); and the chromatin modifiers WHSC1, MLL2, and MEF2B. We also found NOTCH2 mutations as an alternative phenomenon to NOTCH1 mutations in aggressive tumors with a dismal prognosis. Analysis of two simultaneous or subsequent MCL samples by whole-genome/whole-exome (n = 8) or targeted (n = 19) sequencing revealed subclonal heterogeneity at diagnosis in samples from different topographic sites and modulation of the initial mutational profile at the progression of the disease. Some mutations were predominantly clonal or subclonal, indicating an early or late event in tumor evolution, respectively. Our study identifies molecular mechanisms contributing to MCL pathogenesis and offers potential targets for therapeutic intervention.

Evolução Clonal/genética , Variação Genética , Genoma Humano/genética , Linfoma de Célula do Manto/genética , Mutação/genética , Proteínas Mutadas de Ataxia Telangiectasia/genética , Sequência de Bases , Ciclina D1/genética , Estudo de Associação Genômica Ampla , Genômica/métodos , Genótipo , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Linfoma de Célula do Manto/fisiopatologia , Análise em Microsséries , Dados de Sequência Molecular , Receptor Notch2/genética , Receptor 2 Toll-Like/genética
Int J Gynecol Cancer ; 21(8): 1486-90, 2011 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-21892092


BACKGROUND: Women infected with human immunodeficiency virus (HIV) are at increased risk of developing precancerous and cancerous lesions in cervix because of persistence of oncogenic human papillomavirus (HPV) infection. Scarce information about the HPV genotypes attributed to cervical cancer in the HIV-infected population is available, especially in countries with a low prevalence of this pathology. OBJECTIVE: The objective of the study was to assess the prevalence and distribution of HPV types, and the viral integration of HPV-16 and HPV-18 in cervical squamous cell carcinoma of HIV-infected and HIV-negative women. METHODS: A total of 140 formaldehyde-fixed paraffin-embedded specimens from 31 HIV-infected and 109 matched HIV-negative women, with a diagnosis of in situ or invasive cervical carcinoma, were identified between 1987 and 2010 from different hospitals of the Barcelona area, Spain. Human papillomavirus genotyping and integration were analyzed by standardized polymerase chain reaction. RESULTS: Similar prevalence and distribution of HPV genotypes were detected in cervical cancers (in situ and invasive) regardless of HIV condition. The most common types were as follows: HPV-16 (58% in HIV-positive vs 72% in HIV-negative) and HPV-33 (16% vs 8%). In invasive cervical carcinoma, HPV-18 was significantly more prevalent in HIV-positive women (14% vs 1%; P = 0.014). The proportion of samples with integrated forms of HPV-16 (39% vs 45%) and HPV-18 (50% vs 50%) was similar in both groups. CONCLUSIONS: The prevalence and distribution of principal HPV types involved in the carcinogenesis process of the cervix were similar in HIV-infected and noninfected women, although a tendency toward a lower HPV-16 and a higher HPV-18 prevalence in invasive cervical carcinoma was detected in HIV-positive women. Similar percentage of HPV-16 and HPV-18 viral integration was found in formaldehyde-fixed paraffin-embedded specimens of cervical cancer regardless of the HIV infection status.

Carcinoma in Situ/virologia , Infecções por HIV/complicações , Papillomavirus Humano 16/genética , Papillomavirus Humano 18/genética , Infecções por Papillomavirus/complicações , Neoplasias do Colo do Útero/virologia , Adulto , Estudos Transversais , Feminino , Humanos , Pessoa de Meia-Idade , Estudos Retrospectivos