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1.
Int J Gynecol Pathol ; 43(4): 405-413, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38303111

RESUMO

Two etiological pathways have been implicated in the pathogenesis of vulvar squamous cell carcinoma (VSCC): a high-risk human papillomavirus (HPV)-associated route and an HPV-independent pathway characterized by TP53 mutations. Programmed cell death ligand 1 (PD-L1) has become increasingly useful in predicting the response to checkpoint inhibitor therapy in squamous cell carcinomas at various anatomical sites. This study aimed to assess the association between PD-L1 expression and the VSCC subtype to evaluate the utility of PD-L1 in prognostication and therapeutic selection based on HPV status. PD-L1 status was assessed using 3 separate metrics for the extent of PD-L1 staining in various cell types: immune cell score, tumor proportion score (TPS), and combined positive score. The study group consisted of 25 HPV-associated and 28 HPV-independent VSCCs. PD-L1 expression was positive in the majority of VSCCs according to all 3 scoring metrics (84.9% by immune cell score, 77.3% by TPS, and 90.6% by combined positive score). PD-L1 expression was observed in the majority of cases in both groups (60%-96.4%). PD-L1 expression using the TPS method was greater in HPV-independent tumors than in HPV-associated tumors ( P = 0.004), and high PD-L1 expression was also more common in the HPV-independent subtype ( P = 0.016 using the TPS method and P = 0.013 using the combined positive score method). Our findings contribute to the growing evidence that PD-L1 is expressed in the majority of invasive VSCCs, and thus may serve as an attractive therapeutic target. PD-L1 expression is higher in HPV-independent tumors, suggesting that this subtype may be more responsive to PD-L1 inhibitor therapy.


Assuntos
Antígeno B7-H1 , Carcinoma de Células Escamosas , Infecções por Papillomavirus , Neoplasias Vulvares , Humanos , Feminino , Antígeno B7-H1/metabolismo , Neoplasias Vulvares/patologia , Neoplasias Vulvares/virologia , Neoplasias Vulvares/metabolismo , Carcinoma de Células Escamosas/virologia , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/metabolismo , Infecções por Papillomavirus/complicações , Infecções por Papillomavirus/patologia , Pessoa de Meia-Idade , Idoso , Adulto , Biomarcadores Tumorais/metabolismo , Biomarcadores Tumorais/genética , Papillomaviridae , Imuno-Histoquímica , Idoso de 80 Anos ou mais
2.
Int J Gynecol Pathol ; 2024 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-38833724

RESUMO

Atypical polypoid adenomyoma (APA) is a polypoid biphasic lesion of low malignant potential that arises in the lower uterine segment and uterine corpus. The diagnosis of APA is often challenging on biopsy and curettage specimens, and both benign and malignant processes need to be considered in the differential. Stromal expression of p16 and SATB2 have recently been shown to distinguish APA from myoinvasive endometrioid carcinoma. The authors hypothesized that p16 and SATB2 immunohistochemistry could also aid in the distinction of APA from benign adenomyomatous polyp and endometrioid adenomyoma. The study comprised 10 APAs, 7 adenomyomatous polyps, 11 endometrioid adenomyomas, and 10 myoinvasive endometrioid carcinomas. The majority of APAs showed moderate to strong, diffuse p16 and stromal expression. However, most adenomyomatous polyps and endometrioid adenomyomas also exhibited moderate to strong, focal to diffuse p16 stromal expression. SATB2 showed weak to moderate, focal to diffuse expression in the majority of APAs, adenomyomatous polyps and endometrioid adenomyomas. In contrast, p16 and SATB2 were negative to weak and focal in 90% of myoinvasive endometrioid carcinomas. Our findings demonstrate that p16 and SATB2 may be helpful in the differential diagnosis of myoinvasive endometrioid carcinoma and APA while not useful in separating APA from adenomyomatous polyp and endometrioid adenomyoma.

3.
Int J Gynecol Pathol ; 42(1): 1-10, 2023 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-35180768

RESUMO

Gynecologic tract origin of inflammatory myofibroblastic tumor (IMT), a receptor tyrosine kinase fusion driven tumor with malignant potential, is uncommon and mostly involves the uterine corpus where misclassification as a smooth muscle tumor may occur due to overlapping morphologic features. With rare exception, uterine IMT involves ALK rearrangements and exhibits ALK immunoexpression. Molecularly confirmed vulvovaginal IMT has not been reported, but several low-grade mesenchymal tumors in this region exhibit myxoid stroma and/or inflammatory infiltrates that may resemble IMT. The aims of this study were to define the diagnostic specificity of ALK immunoexpression for IMT among a broad spectrum (107 cases) of vulvovaginal mesenchymal tumors in the differential diagnosis of IMT and to report the clinicopathologic features of vulvovaginal IMT identified in our archives or via retrospective ALK staining of otherwise classified vulvovaginal tumors. Review of archives from 5 different centers revealed a single case of vulvar IMT in a 62-yr-old woman. The 2.5 cm well-circumscribed tumor exhibited the typical microscopic features of IMT, namely a loose fascicular distribution of bland spindle cells within a myxoid stroma, accompanied by an infiltrate of plasma cells, lymphocytes, and eosinophils. The tumor cells exhibited expression for smooth muscle actin, desmin, h-caldesmon, and ALK. Break-apart fluorescence in situ hybridization confirmed the presence of ALK rearrangement. The patient did not receive any treatment and is alive without disease 32 mo later. No evidence of ALK expression was detected in any of the other 107 vulvovaginal tumors, which included 14 aggressive angiomyxomas, 2 superficial angiomyxomas, 12 angiomyofibroblastomas, 8 cellular angiofibromas, 15 smooth muscle neoplasms, 10 peripheral nerve sheath tumors, 20 fibroepithelial polyps, and a variety of other low grade mesenchymal tumors. Although vulvovaginal ALK- rearranged IMT is exceedingly rare, the behavior remains to be fully understood. ALK immunohistochemistry, which appears specific for IMT in this anatomic site, is advised in the evaluation of vulvovaginal mesenchymal tumors exhibiting myxoid stroma and/or an inflammatory infiltrate.


Assuntos
Granuloma de Células Plasmáticas , Neoplasias Uterinas , Humanos , Feminino , Hibridização in Situ Fluorescente , Quinase do Linfoma Anaplásico/genética , Estudos Retrospectivos , Biomarcadores Tumorais/metabolismo , Imuno-Histoquímica , Granuloma de Células Plasmáticas/patologia , Neoplasias Uterinas/patologia
4.
Headache ; 60(5): 954-966, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32293736

RESUMO

OBJECTIVE: The objectives of this study are to study osmophobia and odor-triggered headaches among headache pediatric patients. BACKGROUND: Achieving the correct diagnosis for headaches in younger children can be challenging. The presence of osmophobia could constitute a helpful piece of information for making the correct diagnosis of headaches among adults. METHODS: This was a cross-sectional study. Children and adolescents with headaches who were seen consecutively at a pediatric outpatient service and had at least 1 headache attack over the previous 12 months were included. We used a semi-structured questionnaire, Pediatric Migraine Disability Assessment, State-Trait Anxiety Inventory, and Children's Depression Inventory. RESULTS: About 300 patients were included; 253 had migraine, 47 had a tension-type headache; 137 had osmophobia during headaches (135 were migraineurs). "Osmophobia during headaches" for diagnosing migraine: Sensitivity: 54.4% (95% CI: 48.2%-60.5%); specificity: 95.8% (95% CI: 85.8%-98.8%); positive predictive value (PPV): 98.5% (95% CI: 94.8%-99.6%); negative predictive value (NPV): 28.5% (95% CI: 22.0%-36.0%). Osmophobia was associated with higher intensity (OR: 2.90; 95% CI: 1.63, 5.15; P < .001) and duration of the headache (OR: 5.73; 95% CI: 2.29, 14.3; P < .001) and with vomiting (OR: 3.56; 95% CI: 1.83, 6.96; P < .001) (logistic regression). There were 62 patients (all of them migraineurs) with odor-triggered headaches: sensitivity for diagnosing migraine: 24.9% (95% CI: 19.9%-30.6%); specificity: 100% (95% CI: 92.4%-100%), PPV: 100% (95% CI: 94.8%-100%), NPV: 20% (95% CI: 16%-26.0%). Odor-triggered headaches were associated with higher intensity (OR: 3.47; 95% CI: 1.64, 7.35; P = .001) and duration of the headache (OR: 3.28; 95% CI: 1.37, 7.86; P = .001), vomiting (OR: 2.37; 95% CI: 1.19, 4.74; P = .014), and phonophobia (OR: 2.40; 95% CI: 1.08, 5.32; P = .031) (logistic regression). Osmophobia was associated with higher-impact migraine (OR: 4.65; 95% CI: 1.30, 16.6; P = .018) and emergency care (OR: 4.65; 95% CI: 1.81, 12.0; P = .001) (logistic regression). CONCLUSIONS: Osmophobia and odors as triggers for headaches are useful in diagnosing migraine and are markers for the severity of migraine in the pediatric population.


Assuntos
Cefaleia/diagnóstico , Cefaleia/etiologia , Transtornos de Enxaqueca/diagnóstico , Transtornos de Enxaqueca/etiologia , Transtornos do Olfato/complicações , Transtornos do Olfato/diagnóstico , Adolescente , Criança , Estudos Transversais , Feminino , Cefaleia/induzido quimicamente , Humanos , Masculino , Transtornos de Enxaqueca/induzido quimicamente , Odorantes , Transtornos Fóbicos/complicações , Transtornos Fóbicos/diagnóstico , Prevalência , Sensibilidade e Especificidade , Índice de Gravidade de Doença
5.
J Surg Oncol ; 112(6): 669-76, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-26391212

RESUMO

BACKGROUND AND OBJECTIVES: To determine the significance of depth and extent of lymphovascular space invasion (LVSI) on lymph node metastasis and recurrence in endometrial cancer. METHODS: A case-control study was conducted to examine LVSI-positive (n = 70) and LVSI-negative (n = 641) stage I-III endometrial cancer cases that underwent hysterectomy-based surgical staging. The risk of lymph node metastasis and distant recurrence was estimated based on LVSI patterns. RESULTS: In multivariate analysis, deep (>50% invasion), and extensive (≥7 foci/slide) LVSI patterns had a significantly increased risk of lymph node metastasis (incidence 57.6% and 72.7%, odds ratio 33.8 and 49.9, respectively, P < 0.001) as compared to other traditional uterine factors (>50% myometrial tumor invasion, cervical stromal invasion, and adnexal involvement: incidence range 30.4-37.9%, odds ratio range 3.80-7.03). Deep and extensive of LVSI patterns were both significantly correlated to distant recurrence (P < 0.001). Among women who received postoperative chemotherapy, deep and extensive LVSI patterns did not have increased risks for distant recurrence compared to no LVSI (P = 0.47 and 0.32, respectively). Among women who received postoperative radiotherapy, the depth of LVSI was significantly associated with recurrence outside the radiated field (P = 0.02). CONCLUSIONS: Depth and extent of LVSI are important predictors for lymph node metastasis and distant recurrence in endometrial cancer.


Assuntos
Adenocarcinoma de Células Claras/secundário , Cistadenocarcinoma Seroso/secundário , Neoplasias do Endométrio/patologia , Miométrio/patologia , Recidiva Local de Neoplasia/patologia , Células Estromais/patologia , Neoplasias do Colo do Útero/secundário , Adenocarcinoma de Células Claras/mortalidade , Adenocarcinoma de Células Claras/terapia , Estudos de Casos e Controles , Terapia Combinada , Cistadenocarcinoma Seroso/mortalidade , Cistadenocarcinoma Seroso/terapia , Neoplasias do Endométrio/mortalidade , Neoplasias do Endométrio/terapia , Feminino , Seguimentos , Humanos , Metástase Linfática , Pessoa de Meia-Idade , Gradação de Tumores , Invasividade Neoplásica , Recidiva Local de Neoplasia/mortalidade , Recidiva Local de Neoplasia/terapia , Estadiamento de Neoplasias , Prognóstico , Taxa de Sobrevida , Neoplasias do Colo do Útero/mortalidade , Neoplasias do Colo do Útero/terapia
6.
Int J Gynecol Pathol ; 34(1): 57-64, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-25473754

RESUMO

To determine if selected cases of uterine serous carcinoma (USC) arise from tubal rather than endometrial epithelium. Bilateral fallopian tubes from 38 women with pure USC were entirely submitted for histopathologic examination using the protocol Sectioning and Extensively Examining the FIMbria (SEE-FIM). Non-neoplastic endometrium was extensively sampled. Immunohistochemistry for p53 was performed on all paraffin blocks of fallopian tube and non-neoplastic endometrium. Endometrial intraepithelial carcinoma (EIC) was present in 22 cases (58%). Endometrial p53 foci were identified in 3 patients. There were 11 cases (29%) with fallopian tube involvement; 9 of 11 had tubal wall invasion or lymphatic involvement without serous tubal intraepithelial carcinoma (STIC) and were, therefore, classified as metastatic from the endometrium. STIC was identified in 3 patients (8%). There were 3 cases with tubal p53 foci in non-neoplastic epithelium. EIC was present in 58% of patients, further supporting EIC as a precursor lesion to USC. STIC was present in 8%, suggesting that the fallopian tube may in fact represent the primary lesion in a minority of patients with USC. This finding may account for the early multifocal disease distribution observed in these patients.


Assuntos
Carcinoma in Situ/patologia , Endométrio/patologia , Tubas Uterinas/patologia , Neoplasias Císticas, Mucinosas e Serosas/patologia , Lesões Pré-Cancerosas/patologia , Neoplasias Uterinas/patologia , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/metabolismo , Carcinogênese/metabolismo , Carcinogênese/patologia , Carcinoma in Situ/diagnóstico , Carcinoma in Situ/metabolismo , Transformação Celular Neoplásica/metabolismo , Transformação Celular Neoplásica/patologia , Epitélio/patologia , Feminino , Humanos , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Neoplasias Císticas, Mucinosas e Serosas/diagnóstico , Neoplasias Císticas, Mucinosas e Serosas/metabolismo , Lesões Pré-Cancerosas/diagnóstico , Lesões Pré-Cancerosas/metabolismo , Estudos Retrospectivos , Proteína Supressora de Tumor p53/metabolismo , Neoplasias Uterinas/diagnóstico , Neoplasias Uterinas/metabolismo
7.
Rev Gaucha Enferm ; 36(1): 56-61, 2015 Mar.
Artigo em Português | MEDLINE | ID: mdl-26098803

RESUMO

This article aimed to analyze the perception of the nursing team about the care of institutionalized elderly. It consists of a qualitative and exploratory study developed in the six long-term care nursing homes for elderly in the city of João Pessoa/PB, Brazil, from January to June 2013. The sample was comprised 50% of the nurses from all the institutions, totaling 13 participants, whose data were collected through semi-structured questionnaires. Content analysis was used in the study, which enabled the construction of two thematic categories: I) Perceptions of the delivery of care by the nursing staff of the institutions; II) Perceptions of the care activity to be performed by the nursing staff in the institutions. We conclude that the participants are aware of the need for an individualized and systematized care by the nursing staff, aimed to the prevention of diseases, health promotion and active aging.


Assuntos
Atitude do Pessoal de Saúde , Instituição de Longa Permanência para Idosos , Casas de Saúde , Recursos Humanos de Enfermagem , Adulto , Idoso , Feminino , Humanos , Institucionalização , Masculino , Equipe de Enfermagem , Adulto Jovem
8.
Appl Immunohistochem Mol Morphol ; 32(5): 222-228, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38635473

RESUMO

Human epidermal growth factor receptor 2 (HER2) expression has become increasingly helpful in predicting responses to anti-HER2 agents in gynecological cancers. This study retrospectively analyzed HER2 expression in 48 primary ovarian endometrioid carcinomas. HER2 immunohistochemistry was performed using the Ventana platform (Clone 4B5 monoclonal predilute) following the manufacturer's protocol. HER2 expression was equivocal (score 2+) by image analysis in 2 cases (4.17%) based on the breast cancer criteria. Fluorescence in situ hybridization was negative for HER2 amplification in one case (International Federation of Gynecology and Obstetrics, grade 1) and positive in the other (International Federation of Gynecology and Obstetrics, grade 3). Our findings contribute to the growing evidence that HER2 is overexpressed in a small proportion of ovarian endometrioid carcinoma, and thus may serve as a potential therapeutic target in selected cases.


Assuntos
Carcinoma Endometrioide , Neoplasias Ovarianas , Receptor ErbB-2 , Humanos , Feminino , Carcinoma Endometrioide/metabolismo , Carcinoma Endometrioide/patologia , Carcinoma Endometrioide/genética , Carcinoma Endometrioide/diagnóstico , Receptor ErbB-2/metabolismo , Receptor ErbB-2/genética , Pessoa de Meia-Idade , Neoplasias Ovarianas/metabolismo , Neoplasias Ovarianas/patologia , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/diagnóstico , Idoso , Adulto , Estudos Retrospectivos , Amplificação de Genes , Imuno-Histoquímica , Regulação Neoplásica da Expressão Gênica , Hibridização in Situ Fluorescente , Idoso de 80 Anos ou mais
9.
Am J Surg Pathol ; 48(5): 570-580, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38512100

RESUMO

Steroid cell tumors (SCTs) of the ovary are rare and understudied, and as such, uncertainties remain about their malignant potential, as well as clinicopathologic predictors of patient outcome. Based on a multi-institutional cohort of cases, we present findings from the largest study of SCT reported to date. Clinicopathologic data were documented on 115 cases of SCT that were assembled from 17 institutions. The median patient age was 55 years (range: 9 to 84). When measured, preoperative androgen levels were elevated in 84.2% (48/57) of patients. A total of 111 (96.5%) cases were classified as stage I (103 stage IA; 2 stage IB; 6 stage IC). The stage distribution for the remaining 4 patients was as follows: stage II (n = 1), III (n = 3; 1 IIIA, 1 IIIB, 1 IIIC). The median tumor size was 3 cm (range: 0.2 to 22). Cytologic atypia, microscopic tumor necrosis, microscopic tumor hemorrhage, and a mitotic index of >1 mitotic figure/10 high-power fields were present in 52% (60/115), 9.6% (11/115), 37% (43/115), and 19% (22/115) of cases, respectively. Of 115 patients, 7 (6.1%) recurred postexcision, 4 (3.5%) ultimately died of disease, and 10 (8.7%) either recurred, died of disease, or were advanced stage at presentation. The median duration to recurrence postresection was 33 months (range: 23 to 180). Four of the 7 recurrences were stage IA at baseline. Tumor size >4 cm, International Federation of Gynecology and Obstetrics (FIGO) stage ≥IB, tumor necrosis, and tumor hemorrhage were each significantly associated with reduced recurrence-free survival in log-rank tests and univariable Cox models, with age older than 65 years being of marginal significance (hazard ratio [HR]: 5.4, 95% CI: 1.0-30.0, P = 0.05). Multivariable analyses suggested that FIGO stage ≥IB (HR: 27.5, 95% CI: 2.6-290.5), and age older than >65 years (HR: 21.8, 95% CI: 1.6-303.9) were the only parameters that were independently associated with recurrence. Cross-section analyses showed that tumor necrosis, tumor hemorrhage, and larger tumor size were significantly associated with a FIGO stage ≥IB status, which bolstered the conclusion that they are not independent predictors of recurrence. In summary, <10% of SCTs are clinically malignant, a substantially lower frequency than has previously been reported in the literature. Clinicopathologic predictors of patient outcomes that are prospectively applicable in practice could not be definitively established. Recurrences may occur many years (up to 15 y in this study) after primary resection, even in stage IA cases.


Assuntos
Neoplasias Ovarianas , Tumores do Estroma Gonadal e dos Cordões Sexuais , Feminino , Humanos , Criança , Adolescente , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Estadiamento de Neoplasias , Neoplasias Ovarianas/patologia , Tumores do Estroma Gonadal e dos Cordões Sexuais/patologia , Hemorragia/patologia , Necrose/patologia , Esteroides , Prognóstico
10.
Nat Genet ; 55(2): 255-267, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36624343

RESUMO

Endometriosis is a common condition in women that causes chronic pain and infertility and is associated with an elevated risk of ovarian cancer. We profiled transcriptomes of >370,000 individual cells from endometriomas (n = 8), endometriosis (n = 28), eutopic endometrium (n = 10), unaffected ovary (n = 4) and endometriosis-free peritoneum (n = 4), generating a cellular atlas of endometrial-type epithelial cells, stromal cells and microenvironmental cell populations across tissue sites. Cellular and molecular signatures of endometrial-type epithelium and stroma differed across tissue types, suggesting a role for cellular restructuring and transcriptional reprogramming in the disease. Epithelium, stroma and proximal mesothelial cells of endometriomas showed dysregulation of pro-inflammatory pathways and upregulation of complement proteins. Somatic ARID1A mutation in epithelial cells was associated with upregulation of pro-angiogenic and pro-lymphangiogenic factors and remodeling of the endothelial cell compartment, with enrichment of lymphatic endothelial cells. Finally, signatures of ciliated epithelial cells were enriched in ovarian cancers, reinforcing epidemiologic associations between these two diseases.


Assuntos
Endometriose , Transcriptoma , Humanos , Feminino , Transcriptoma/genética , Endometriose/genética , Endometriose/metabolismo , Células Endoteliais/metabolismo , Células Epiteliais/metabolismo , Epitélio
11.
Ecohealth ; 20(4): 355-361, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38236519

RESUMO

Rabies transmitted by wildlife is the main source of human rabies mortality in Latin America and considered an emerging disease. The common marmoset Callithrix jacchus of Brazil is the only known primate reservoir of rabies worldwide. We tested whether alive free-ranging C. jacchus were exposed to rabies in four northeast states that have previously reported rabies-positive dead C. jacchus (Pernambuco and Bahia) or not (Paraíba and Rio Grande do Norte). Our results show no evidence of rabies antibodies or infection in the sampled C. jacchus, suggesting that apparently healthy marmosets are not widely exposed to rabies over their natural range.


Assuntos
Vírus da Raiva , Raiva , Animais , Humanos , Raiva/veterinária , Callithrix , Brasil , Animais Selvagens
12.
Gynecol Oncol ; 127(3): 525-31, 2012 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-22940491

RESUMO

OBJECTIVE: To determine the reliability of intraoperative frozen sections (IFSs) for surgical staging of endometrial cancer (EC). METHODS: Data were collected prospectively on 784 consecutive patients with EC who were undergoing a hysterectomy at our institution from January 1, 2004, to December 31, 2008. The need for surgical staging was decided through IFS using 4 variables: tumor size, histologic grade, histologic subtype, and depth of myometrial invasion (MI). The IFS results were compared with the permanent paraffin sections (PSs) to assess for discordances. RESULTS: In 30 of the 784 cases (4%), the PS pathology report was amended with discordant results. In addition, a definitive diagnosis of the 4 parameters was deferred to PS in 53 cases (7%), of which 30 (4%) were concordant and 23 (3%) were discordant. IFS-related deviations from the prescribed surgical algorithm occurred in 10 cases (1.3%; 95% confidence interval, 0.6%-2.3%). Of these 10 cases, 3 were amendments after PS review and 7 were IFS deferrals for definitive PS interpretation. CONCLUSIONS: Clinically significant discordance between IFS and PS occurred in only 1.3% of cases. Despite skepticism expressed in the medical literature, IFS provides highly reliable data to guide intraoperative treatment decisions at institutions with sufficient pathologic expertise.


Assuntos
Neoplasias do Endométrio/patologia , Neoplasias do Endométrio/cirurgia , Secções Congeladas , Feminino , Humanos , Gradação de Tumores , Invasividade Neoplásica , Estadiamento de Neoplasias , Estudos Prospectivos , Reprodutibilidade dos Testes
13.
Int J Gynecol Pathol ; 31(3): 195-205, 2012 May.
Artigo em Inglês | MEDLINE | ID: mdl-22498935

RESUMO

Endometrial cancer is associated with numeric and structural chromosomal abnormalities, microsatellite instability (MSI), and alterations that activate oncogenes and inactivate tumor suppressor genes. The aim of this study was to characterize a set of endometrial cancers using multiple molecular genetic and immunohistochemical techniques. Ninety-six cases were examined for genomic alterations by MSI, MLH1 promoter hypermethylation, p53 and mismatch repair protein expression (MLH1, MSH2, MSH6, PMS2), and PTEN, PIK3CA, KRAS, and BRAF mutation analysis. At least 1 alteration was identified in 48 of 87 (55%) specimens tested for PTEN, making it the most common abnormality in this study. A PIK3CA alteration was observed in 16 (17%) specimens. Twenty-nine of 94 (31%) MSI tested tumors exhibited an MSI-H phenotype. Of the 29 MSI-H cases, 24 (83%) were positive for methylation of the MLH1 promoter region. Twenty-three (82%) of the 28 MSI-H cases with immunohistochemistry results showed loss of expression of MLH1/PMS2 (n=19), MSH2/MSH6 (n=2), or MSH6 only (n=2). Of the 19 MSI-H cases with loss of MLH1/PMS2 on immunohistochemistry, 18 were positive, and 1 was equivocal for MLH1 promoter hypermethylation. Twelve of 94 cases (13%) analyzed for KRAS mutations were found to have a mutation. No BRAF V600E mutations were indentified. This study provides a comprehensive molecular genetic analysis of commonly analyzed targets in a large cohort of endometrial cancers.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/genética , Reparo de Erro de Pareamento de DNA/genética , DNA de Neoplasias/genética , Neoplasias do Endométrio/genética , Hidrolases/genética , Instabilidade de Microssatélites , Proteínas Nucleares/genética , Fosfotransferases/genética , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Idoso , Classe I de Fosfatidilinositol 3-Quinases , Estudos de Coortes , Análise Mutacional de DNA , Neoplasias do Endométrio/metabolismo , Feminino , Humanos , Metilação , Proteína 1 Homóloga a MutL , Mutação/genética , Proteínas Nucleares/metabolismo , PTEN Fosfo-Hidrolase/genética , Fosfatidilinositol 3-Quinases/genética , Proteínas Proto-Oncogênicas/genética , Proteínas Proto-Oncogênicas B-raf/genética , Proteínas Proto-Oncogênicas p21(ras) , Estudos Retrospectivos , Proteína Supressora de Tumor p53/metabolismo , Proteínas ras/genética
14.
Front Vet Sci ; 9: 846994, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35601400

RESUMO

Post-exposure prophylaxis (PEP) is necessary to prevent the fatal onset of rabies but requires optimization to avoid overuse in populations at risk of rabies. In Brazil, the incidence of dog bites remains high, with almost half of dog-bite patients not receiving the PEP recommended by the Ministry of Health guidelines between 2008 and 2017. In this study, we aimed to identify the factors that limit the appropriate prescribing of PEP by interviewing health professionals responsible for PEP administration and completion of the 'Information System on Diseases of Compulsory Declaration' (SINAN) form reporting human anti-rabies care for patients seeking health care after a dog bite. We conducted 147 questionnaires (45 questions each) in three Brazilian states (i.e., Rio Grande do Sul, Santa Catarina, Rio Grande do Norte) including questions related to the criteria used by professionals to classify a dog as "suspect" or "rabid", knowledge on PEP prescription guidelines, SINAN and communication with veterinarians. Our analyses showed that most health professionals delivering PEP in these three states struggle to identify a rabies "suspect" dog according to the Ministry of Health guidelines, and to indicate the adequate PEP regimen, with only 11% of professionals prescribing the appropriate PEP under various dog-bite patient scenarios. PEP knowledge score was higher among professionals trained on PEP guidelines and working in facilities with the highest incidence of dog bites. In contrast, PEP knowledge scores did not vary significantly between states, and were not correlated to the professional's level of experience, the number of colleagues available at the health unit or the professional's confidence on prescribing appropriate PEP. Our results suggest that knowledge gaps in PEP administration among health professionals of Brazil can be reduced by implementing training programs to differentiate among rabies risk scenarios, prescribe the corresponding appropriate PEP and improve communication between health and veterinary authorities.

15.
Genes Chromosomes Cancer ; 49(7): 630-4, 2010 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-20461755

RESUMO

Endometriosis is a common gynecologic disorder characterized by ectopic endometrium associated with pelvic pain and infertility. The pathogenesis of endometriosis is unclear, and several genetic, endocrine, immune, and environmental agents have been studied as putative causative factors. However, consistent somatic genetic alterations have not been identified. Rarely, endometriosis presents as a mass lesion with an infiltrative pattern reminiscent of malignancy. We describe cytogenetic and molecular cytogenetic findings of mass-forming endometriosis. The index case of pulmonary endometriosis underwent conventional and molecular cytogenetics analysis. In addition, 16 cases of mass-forming endometriosis, 11 cases of usual endometriosis, and six endometriomas were investigated by fluorescence in situ hybridization (FISH) for HMGA1 and HMGA2 loci, performed on paraffin-embedded thin tissue sections with custom-designed probes. The index patient had an endometriotic lung nodule, with a 46,XX, t(5;6)(q13;p21) karyotype and HMGA1 rearrangement by FISH. A second patient had decidualized endometriosis forming a large abdominal mass and HMGA1 rearrangement by FISH. Of the 15 other cases of mass-forming endometriosis, one had HMGA1 rearrangement and two had HMGA2 rearrangement. The rearrangements were found in the stromal component exclusively. None of the usual endometriosis cases or endometriomas had HMGA1 or HMGA2 rearrangements. In conclusion, mass-forming endometriosis is an uncommon subset of endometriosis that harbors HMGA1 or HMGA2 rearrangements in up to 29% of cases. The present findings support the concept that endometriosis is clonal and that rearrangement of HMGA genes likely contributes to its pathogenesis.


Assuntos
Endometriose/genética , Proteínas HMGA/genética , Proteína HMGA2/genética , Fenômenos Bioquímicos , Análise Citogenética , Formas de Dosagem , Feminino , Proteínas HMGA/metabolismo , Proteína HMGA2/metabolismo , Humanos , Cariotipagem , Neoplasias Pulmonares/genética , Dor Pélvica/genética
16.
Dement Neuropsychol ; 15(4): 548-549, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-35509806

RESUMO

We reported a case of a 61-year-old male patient with anacusis, cerebellar syndrome, myoclonus, and frontal signs. The brain magnetic resonance imaging showed bilateral striated hyperintensity of the fluid-attenuated inversion recovery and restricted diffusion in the diffusion-weighted imaging and hypointense areas corresponding to the apparent diffusion coefficient in the cerebral cortex. The autopsy revealed positive immunohistochemistry for the PrPSc protein. Creutzfeldt-Jakob disease presenting with hearing loss is unusual.


Relatamos o caso de um paciente do sexo masculino, 61 anos, com anacusia, síndrome cerebelar, mioclonia e sinais frontais. A ressonância magnética cerebral mostrou hiperintensidade estriada bilateral do fluid-attenuated inversion recovery (FLAIR) e difusão restrita no diffusion-weighted imaging (DWI) e áreas hipointensas correspondendo ao coeficiente de difusão aparente no córtex cerebral. A autópsia revelou imuno-histoquímica positiva para a proteína PrPSc. A doença de Creutzfeldt-Jakob que se apresenta com perda auditiva é incomum.

17.
Rev Esc Enferm USP ; 55: e20200528, 2021.
Artigo em Inglês, Português | MEDLINE | ID: mdl-34448805

RESUMO

OBJECTIVE: To analyze the risk of violence associated to functional capacity and sociodemographic characteristics of hospitalized elderly. METHOD: Quantitative, cross-sectional, multicenter study conducted with elderly receiving care at university hospitals of the municipalities of João Pessoa and Campina Grande, in the state of Paraíba, Brazil. The scales Katz and Hwalek-Sengstock Elder Abuse Screening Test were applied. The data was analyzed through descriptive and inferential statistics using Chi-squared Pearson test, Spearman correlation test, and multiple logistic regression. RESULTS: The participating elderly amounted to 323. The risk of violence was predominant among female elders aged 60 to 70 who are unable to read or write, live with someone, perform no labor activity, and whose income is higher than a minimum wage. Elders who were dependent for basic and instrumental activities presented a 2.11 score (Confidence Interval = 1.22-3.64; p = 0.000) and 1.70 (1.01-2.85; p = 0.044) and a higher risk of violence. CONCLUSION: Elders who depended on other people to perform both complex and basic activities are the most exposed to situations of violence.


Assuntos
Abuso de Idosos , Idoso , Brasil/epidemiologia , Estudos Transversais , Feminino , Humanos , Modelos Logísticos , Violência
18.
J Biomech ; 122: 110478, 2021 06 09.
Artigo em Inglês | MEDLINE | ID: mdl-33964576

RESUMO

Pedaling asymmetry is claimed as a factor of influence on injury and performance. However, the evidence is still controversial. Most previous studies determined peak torque asymmetries, which in our understanding does not consider the pattern of movement like torque profiles. Here we demonstrate that asymmetries in pedaling torque at different exercise intensities can be better described when the torque profiles are considered using functional analysis of variance than when only the peak values are analyzed. We compared peak torques and torque curves recorded while cyclists pedaled at submaximal intensities of 60%, 80%, and 95% of the maximal power output and compared data between the preferred and non-preferred legs. ANOVA showed symmetry or rather no difference in the amount of peak torque between legs, regardless of pedaling intensity. FANOVA, on the other hand, revealed significant asymmetries between legs, regardless of cycling intensity, apparently for different sections of the cycle, however, not for peak torque, either. We conclude that pedaling asymmetry cannot be quantified solely by peak torques and considering the analysis of the entire movement cycle can more accurately reflect the biomechanical movement pattern. Therefore, FANOVA data analysis could be an alternative to identify asymmetries. A novel approach as described here might be useful when combining kinetics assessment with other approaches like EMG and kinematics and help to better understand the role of pedaling asymmetries for performance and injury risks.


Assuntos
Ciclismo , Análise de Dados , Fenômenos Biomecânicos , Perna (Membro) , Músculo Esquelético , Torque
19.
Cell Rep ; 35(2): 108978, 2021 04 13.
Artigo em Inglês | MEDLINE | ID: mdl-33852846

RESUMO

The human fallopian tube harbors the cell of origin for the majority of high-grade serous "ovarian" cancers (HGSCs), but its cellular composition, particularly the epithelial component, is poorly characterized. We perform single-cell transcriptomic profiling of around 53,000 individual cells from 12 primary fallopian specimens to map their major cell types. We identify 10 epithelial subpopulations with diverse transcriptional programs. Based on transcriptional signatures, we reconstruct a trajectory whereby secretory cells differentiate into ciliated cells via a RUNX3high intermediate. Computational deconvolution of advanced HGSCs identifies the "early secretory" population as a likely precursor state for the majority of HGSCs. Its signature comprises both epithelial and mesenchymal features and is enriched in mesenchymal-type HGSCs (p = 6.7 × 10-27), a group known to have particularly poor prognoses. This cellular and molecular compendium of the human fallopian tube in cancer-free women is expected to advance our understanding of the earliest stages of fallopian epithelial neoplasia.


Assuntos
Subunidade alfa 3 de Fator de Ligação ao Core/genética , Endometriose/genética , Leiomioma/genética , Fator de Transcrição PAX8/genética , Fatores de Transcrição SOXF/genética , Transcriptoma , Adulto , Diferenciação Celular , Linhagem Celular Tumoral , Subunidade alfa 3 de Fator de Ligação ao Core/metabolismo , Endometriose/metabolismo , Endometriose/patologia , Endometriose/cirurgia , Células Epiteliais/metabolismo , Células Epiteliais/patologia , Transição Epitelial-Mesenquimal , Tubas Uterinas/metabolismo , Tubas Uterinas/patologia , Tubas Uterinas/cirurgia , Feminino , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Humanos , Leiomioma/metabolismo , Leiomioma/patologia , Leiomioma/cirurgia , Pessoa de Meia-Idade , Fator de Transcrição PAX8/metabolismo , Fatores de Transcrição SOXF/metabolismo , Transdução de Sinais , Análise de Célula Única
20.
Rev Bras Enferm ; 74Suppl 2(Suppl 2): e20200628, 2021.
Artigo em Inglês, Português | MEDLINE | ID: mdl-34287499

RESUMO

OBJECTIVE: to clinically validate the nursing diagnosis of NANDA-I Frail Elderly Syndrome in hospitalized elderly. METHOD: a methodological study, guided by the STROBE instrument, composed of 40 elderly people admitted to a teaching hospital in Paraíba, Brazil. The last phase of Hoskins' Nursing Diagnostic Validation Model: clinical validation was adopted. Data collection took place from August to December 2018. The data were analyzed using univariate descriptive statistics. It was approved by the hospital's ethics and research committee. RESULTS: nine defining characteristics were validated; seven risk factors; six populations at risk and two associated conditions. CONCLUSION: the validation of the nursing diagnosis of the Frail Elderly Syndrome in our socio-cultural context was considered appropriate, being an important step for critical thinking that underlies the decision-making of nurses in the care of the frail elderly, as well as professional practice.


Assuntos
Diagnóstico de Enfermagem , Terminologia Padronizada em Enfermagem , Idoso , Brasil , Idoso Fragilizado , Humanos , Fatores de Risco
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