RESUMO
Atopic dermatitis (AD) is a chronic inflammatory skin disease of very high prevalence, especially in childhood, with no specific treatment or cure. As its pathogenesis is complex, multifactorial and not fully understood, further research is needed to increase knowledge and develop new targeted therapies. We have recently demonstrated the critical role of NAD+ and poly (ADP-ribose) (PAR) metabolism in oxidative stress and skin inflammation. Specifically, we found that hyperactivation of PARP1 in response to DNA damage induced by reactive oxygen species, and fueled by NAMPT-derived NAD+, mediated inflammation through parthanatos cell death in zebrafish and human organotypic 3D skin models of psoriasis. Furthermore, the aberrant induction of NAMPT and PARP activity was observed in the lesional skin of psoriasis patients, supporting the role of these signaling pathways in psoriasis and pointing to NAMPT and PARP1 as potential novel therapeutic targets in treating skin inflammatory disorders. In the present work, we report, for the first time, altered NAD+ and PAR metabolism in the skin of AD patients and a strong correlation between NAMPT and PARP1 expression and the lesional status of AD. Furthermore, using a human 3D organotypic skin model of AD, we demonstrate that the pharmacological inhibition of NAMPT and PARP reduces pathology-associated biomarkers. These results help to understand the complexity of AD and reveal new potential treatments for AD patients.
Assuntos
Dermatite Atópica , Psoríase , Animais , Humanos , Inflamação , NAD/metabolismo , Poli(ADP-Ribose) Polimerase-1/metabolismo , Poli Adenosina Difosfato Ribose/metabolismo , Poli ADP Ribosilação , Inibidores de Poli(ADP-Ribose) Polimerases/farmacologia , Psoríase/etiologia , Peixe-Zebra/metabolismoRESUMO
We describe a rare case of complete hydatidiform mole with twin live fetus (CHMTF) confirmed by histopathology, flow cytometry and polymerase chain reaction techniques. No malformations were observed, fetal karyotype was normal and ß-human chorionic gonadotropin levels were high (>100,000 IU/ml). The patient was informed of the risks and decided to continue with the pregnancy, but at week 15, she had to undergo hysterectomy due to uterine rupture. She subsequently developed persistent trophoblastic disease (PTD) with pulmonary metastases that required treatment with polychemotherapy. Patients with CHMTF should be informed of all known risks, including the considerable risk of PTD, which is similar to or, even higher than that associated with a singleton complete mole. The risk does not appear to be increased by continuing the pregnancy. Because so few series have been published, there is a lack of evidence-based clinical management guidelines. To our knowledge, this is the first report of uterine rupture in CHMTF.
Assuntos
Doença Trofoblástica Gestacional/patologia , Mola Hidatiforme/patologia , Gravidez de Gêmeos , Neoplasias Uterinas/patologia , Ruptura Uterina/cirurgia , Adulto , Gonadotropina Coriônica/sangue , Feminino , Humanos , Histerectomia/métodos , Neoplasias Pulmonares/secundário , Neoplasias Pulmonares/terapia , Repetições de Microssatélites/genética , Gravidez , Resultado do TratamentoRESUMO
We describe a rare case of complete hydatidiform mole with twin live fetus (CHMTF) confirmed by histopathology, flow cytometry, and polymerase chain reaction techniques. No malformations were observed, fetal karyotype was normal and ß-human chorionic gonadotropin levels were increased (>100,000 IU/ml). Once the patient had been informed of the risks, it was decided to continue the pregnancy, but termination of pregnancy was necessary at week 13 + 5 due to maternal complications consisting of hyperthyroidism, hypertension and vaginal bleeding, followed by persistent trophoblastic disease (PTD). Patients diagnosed with CHMTF should be informed of all known risks, including the considerable risk of PTD, which is similar to - or according to some reports - even higher than that associated with a singleton complete mole and is not increased by continuing pregnancy. Due to the low number of series published, evidence-based clinical management guidelines are lacking.
Assuntos
Mola Hidatiforme/diagnóstico por imagem , Gravidez de Gêmeos , Adulto , Diagnóstico Diferencial , Diploide , Feminino , Humanos , Mola Hidatiforme/complicações , Mola Hidatiforme/terapia , Gravidez , Fatores de Risco , UltrassonografiaRESUMO
Hepatoportal sclerosis (HPS) is characterized by presinusoidal intrahepatic portal hypertension associated with splenomegaly and anemia in patients with non-cirrhotic liver. Liver biopsy is essential, especially to rule out other processes. Being a disease of unknown etiology, the majority of cases have been described in eastern countries. However, it may be an underdiagnosed disease in the West. Symptoms are related to portal hypertension and the clinical spectrum is wide, ranging from anemia with normal liver function tests to bleeding due to esophageal varices. Treatment is directed to the complications and the prognosis is better than in patients with cirrhosis.We report three cases of HPS presenting at different clinical stages and the findings of liver biopsies, the clinical outcomes and a review of scientific literature.
Assuntos
Hipertensão Portal/diagnóstico , Cirrose Hepática/diagnóstico , Pancitopenia/diagnóstico , Esplenomegalia/diagnóstico , Adulto , Biópsia , Humanos , Hipertensão Portal/patologia , Fígado/patologia , Cirrose Hepática/patologia , Masculino , Pessoa de Meia-Idade , Pancitopenia/patologia , Esplenomegalia/patologia , Hipertensão Portal não Cirrótica IdiopáticaRESUMO
NK and CD8+ T cells are the main cytolytic effectors involved in innate and adaptive tumor immune surveillance, respectively. Although their educational pathways differ, similarities in their development and function suggest that CD8+ T lymphocytes could be sensitive to NK cell licensing signals, which might influence their antitumor response. To demonstrate this hypothesis, we retrospectively evaluated the impact that NK cell licensing interactions have on the expression of CD226 on CD8+ T lymphocytes and on the survival of patients with different hematopoietic and solid cancers (n = 1,023). Prospectively, we analyzed by multiparametric flow cytometry the anti-CD3/CD28-induced proliferation and immune-receptor expression of purified CD8+ T lymphocytes from healthy donors (n = 17) with different combinations of NK cell licensing ligands. Results show that methionine/threonine (M/T) dimorphism at position -21 of the HLA-B leader peptide, but not other HLA class-I dimorphisms involved in the education of NK cells (HLA-C1/C2 or HLA-Bw4), is associated with greater survival and expression of CD226 in cancer patients, which was proportional to the number of methionines present in their genotype. CD8+ T lymphocytes from healthy donors with -21 M showed higher proliferation rates and lower expression of TIGIT after in vitro stimulation. Therefore, CD8+ T lymphocytes, like NK cells, appear to be sensitive to the -21 M/T dimorphism of HLA-B leader peptide, which results in the modulation of CD226 in vivo and the proliferation and expression of TIGIT after in vitro stimulation, all of which could be related to their immune-surveillance capacity and the survival of cancer patients.
Assuntos
Linfócitos T CD8-Positivos , Neoplasias , Antígenos de Histocompatibilidade Classe I , Humanos , Neoplasias/genética , Estudos Retrospectivos , Antígenos HLA-ERESUMO
BACKGROUND: Bladder cancer (BC) is highly immunogenic. Bacillus Calmette-Guérin (BCG) immunotherapy offers the best results in non-muscle-invasive BC (NMIBC). Natural killer cells (NKcs) play decisive roles in BCG-mediated immune response and in general cancer immune-surveillance. OBJECTIVE: To analyze killer-cell immunoglobulin-like receptors (KIRs), their human leukocyte antigen class-I (HLA-I) ligands, and the expression of DNAX Accessory Molecule-1 (DNAM-1/CD226) on peripheral blood (PB) NKcs, to identify useful predictive biomarkers in BC. DESIGN, SETTING, AND PARTICIPANTS: KIR/HLA-ligand genotypes were compared between 132 BC, 201 other solid cancers, 164 plasma cell disorders, and 615 healthy Caucasoid controls. CD226 expression was evaluated by flow cytometry. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: KIR/HLA-I interactions and CD226 expression on NKcs (CD226high or CD226low) were compared across study groups, cancer stages, treatments, and progression-free and overall survival of patients, using chi-square, analysis of variance/post hoc, Kaplan-Meier/log-rank, and regression analyses. RESULTS AND LIMITATIONS: Three immunological risk groups were identified: low risk (KIR2DL1-L2+L3-/C1C1- and KIR2DL1+L2+L3+/C1C1+), intermediate risk (rest), and high risk (KIR2DL5+/HLA-C*16+ and KIR2DL1+L2+L3-), which displayed different 10-yr progression-free rates (83.3%, 48.6%, and 0%, respectively; p<0.001) and survival rates (83.3%, 54.3%, and 6.2%, respectively; p<0.001) for muscle-invasive T2/T4, and 10-yr progression-free rates (100%, 81.6%, and 50%, respectively; p<0.05) for NMIBC-T1 treated with BCG. Immunological risk stratification had an independent prognostic value to just histological staging for survival (hazard ratio=2.93, p<0.00001, Harrell C-statistic=0.779). CD226 expression on PB NKcs improved immunological stratification in intermediate-risk T1-T4 BC patients, with survival rates of 94.1% and 66.7% for CD226high and CD226low (p<0.05), respectively. CONCLUSIONS: Immunological risk stratification will complement BC histopathology to improve risk stratification and guide the selection of personalized treatments. Understanding of the molecular mechanisms of NKc tumor immune surveillance will enable the development of future NKc-based therapies. PATIENT SUMMARY: This work describes a peripheral blood test that aids in our understanding of the immune defense mechanisms against bladder cancer, is useful for classifying patient risk, and will guide personalized treatments.
Assuntos
Neoplasias da Bexiga Urinária , Biomarcadores , Humanos , Células Matadoras Naturais , Prognóstico , Medição de Risco , Neoplasias da Bexiga Urinária/diagnóstico , Neoplasias da Bexiga Urinária/genética , Neoplasias da Bexiga Urinária/terapiaRESUMO
OBJECTIVE: To describe an extremely rare case of a partial hydatidiform mole with a normal fetus. The etiology and clinical management of this entity are discussed. METHOD: Case report. RESULTS: We describe a rare case of partial mole and a living fetus of diploid karyotype and biparental origin confirmed by flow cytometry and PCR techniques. No malformations were observed, beta-hCG levels were high (>100,000 mIU/ml) and persistent trophoblastic disease did eventually occur. CONCLUSION: A suspected partial mole on ultrasound with increased beta-hCG and a sonographically normal living fetus of a diploid karyotype poses a dilemma for clinical management. Termination of pregnancy is not indicated if the fetus is normal; in fact, continuation to birth is possible in nearly 60% of cases with no increase in maternal risks when the patient is closely monitored after birth until beta-hCG is negative. In the case presented, however, a spontaneous abortion occurred at 21 weeks' gestation, possibly as a result of the amniocentesis.
Assuntos
Diploide , Mola Hidatiforme/diagnóstico por imagem , Aborto Espontâneo , Adulto , Gonadotropina Coriônica Humana Subunidade beta/sangue , Feminino , Feto , Humanos , Mola Hidatiforme/sangue , Gravidez , UltrassonografiaRESUMO
Therapies using NK cells (NKc) expanded/activated ex vivo or stimulated in vivo with new immunostimulatory agents offer alternative opportunities for patients with recurrent/refractory tumors, but relevant biomarkers to guide the selection of patients are required for optimum results. Overall survival of 249 solid cancer patients was evaluated in relation to the genetics and/or the expression on peripheral blood NKcs of inhibitory and activating killer-cell immunoglobulin-like receptors (iKIR and aKIR, respectively), HLA class I ligands, CD226 (also known as DNAM-1), and NKG2A. Compared with patients with higher expression, patients with low expression of CD226 on total NKcs showed shorter mean overall survival (60.7 vs. 98.0 months, P < 0.001), which was further reduced in presence of telomeric aKIRs (KIR2DS1-DS5 and/or KIR3DS1, 31.6 vs. 96.8 months, P < 0.001). KIR2DL2/S2+, KIR3DL1+, KIR2DL1+, and KIR2DL3+ NKc subsets in the presence of their cognate ligands primarily contributed to shortening patients' overall survival by increasing the sensitivity to CD226 downmodulation in aKIR-rich telomeric genotypes. In patients with high tumor burden who died during the follow-up period, aKIR-rich telomeric genotypes were associated with: (i) specific downmodulation of CD226 on educated NKcs but not on CD8+ T cells or uneducated NKcs, (ii) lower expression of CD226 and higher expression of NKG2A on aKIR+ NKcs, and (iii) lower numbers of total CD56dim NKcs. The reduced expression of CD226 on NKcs with aKIR-rich genotypes may be a biomarker indicative of NKc hyporesponsiveness in patients that could benefit from new NKc immune-stimulatory therapies.
Assuntos
Antígenos de Diferenciação de Linfócitos T/genética , Vigilância Imunológica , Células Matadoras Naturais/imunologia , Células Matadoras Naturais/metabolismo , Neoplasias/etiologia , Neoplasias/metabolismo , Receptores KIR/genética , Antígenos de Diferenciação de Linfócitos T/metabolismo , Biomarcadores , Linhagem Celular Tumoral , Citometria de Fluxo , Regulação Neoplásica da Expressão Gênica , Genótipo , Antígenos HLA/genética , Antígenos HLA/imunologia , Humanos , Ligantes , Neoplasias/patologia , Prognóstico , Ligação Proteica , Receptores KIR/metabolismoRESUMO
INTRODUCTION: Small GIST (<2 cm) are tumors whose biological behavior is benign and frequently involutes. Despite their increasing incidence, few studies have addressed the characteristics of these GIST. The aim of this work is to clarify the management of this entity. PATIENTS AND METHOD: The characteristics of ≤2 cm GIST were initially described, and then compared with those >2 cm. This series comprises 104 patients and they were divided according to tumor size in 4 groups: tumors which are ≤2 cm (group 1, G1), >2 and ≤ 5 cm (G2), >5 and ≤ 10 cm (G3) and >10 cm (G4). RESULTS AND DISCUSSION: Most of small GIST were asymptomatic and incidental, and were located in the stomach. There is an association between patients with associated tumors and asymptomatic GIST. A high overall mortality rate of up to 40% is observed being disease-specific mortality 4.5%. The disease-specific mortality increases proportionally with size. The overall survival (OS) at 5 years are lower for both <2 cm (61%) and >10 cm (53%) than the rest (85-91%). When analyzing the impact of tumor association on <2 cm GIST, we observed that the OS of patients with non-associated tumors was much higher than in the associated ones (90% vs 32% at 5 years, respectively), while no differences were observed in the disease specific survival. CONCLUSIONS: Small GIST are tumors that are very often incidentally discovered in the course of complementary examinations. Its prognosis is very good, but it depends on the associated tumor.
Assuntos
Neoplasias Gastrointestinais/patologia , Tumores do Estroma Gastrointestinal/patologia , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Causas de Morte , Neoplasias do Colo/mortalidade , Neoplasias do Colo/patologia , Neoplasias Duodenais/mortalidade , Neoplasias Duodenais/patologia , Neoplasias Esofágicas/mortalidade , Neoplasias Esofágicas/patologia , Feminino , Neoplasias Gastrointestinais/mortalidade , Tumores do Estroma Gastrointestinal/mortalidade , Humanos , Masculino , Pessoa de Meia-Idade , Mortalidade , Estadiamento de Neoplasias , Prognóstico , Neoplasias Retais/mortalidade , Neoplasias Retais/patologia , Estudos Retrospectivos , Fatores Sexuais , Neoplasias Gástricas/mortalidade , Neoplasias Gástricas/patologia , Carga TumoralRESUMO
Natural killer cell (NKc)-based therapies offer promising outcomes in patients with tumors, but they could improve with appropriate selection of donors and optimization of methods to expand NKcs in vitro Education through licensing interactions of inhibitory killer cell immunoglobulin-like receptors (iKIR) and NKG2A with their cognate HLA class-I ligands optimizes NKc functional competence. This work has evaluated the role of licensing interactions in NKc differentiation and the survival of cancer patients. We have analyzed KIR and KIR-ligand genes, and the expression of activating (CD16 and DNAM-1/CD226) and inhibitory (NKG2A and iKIRs) receptors on peripheral blood NKcs in 621 healthy controls and 249 solid cancer patients (80 melanoma, 80 bladder, and 89 ovarian). Licensing interactions upregulated the expression of activating CD226, reduced that of iKIR receptors, and shifted the CD226/iKIR receptor ratio on NKc membranes to activating receptors. A high tumor burden decreased CD226 expression, reduced the ratio of CD226/iKIR, and negatively affected patient survival. The progression-free survival (38.1 vs. 67.0 months, P < 0.002) and overall survival (56.3 vs. 99.6 months, P < 0.00001) were significantly shorter in patients with lower expression of CD226 on NKcs. Hence, transformed cells can downmodulate these licensing-driven receptor rearrangements as a specific mechanism to escape NKc immune surveillance. Our results suggest the importance of the CD226/iKIR receptor ratio of NKcs induced by licensing interactions as critical determinants for solid cancer immune surveillance, and may provide predictive biomarkers for patient survival that may also improve the selection of donors for NKc immunotherapy.
Assuntos
Antígenos de Diferenciação de Linfócitos T/metabolismo , Vigilância Imunológica , Células Matadoras Naturais/imunologia , Receptores KIR/metabolismo , Idoso , Antígenos de Diferenciação de Linfócitos T/imunologia , Biomarcadores Tumorais/imunologia , Estudos de Casos e Controles , Feminino , Antígenos HLA-C/genética , Humanos , Células Matadoras Naturais/metabolismo , Masculino , Melanoma/genética , Melanoma/imunologia , Melanoma/mortalidade , Pessoa de Meia-Idade , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/imunologia , Neoplasias Ovarianas/mortalidade , Estudos Prospectivos , Receptores KIR/genética , Receptores KIR/imunologia , Análise de Sobrevida , Neoplasias da Bexiga Urinária/genética , Neoplasias da Bexiga Urinária/imunologia , Neoplasias da Bexiga Urinária/mortalidadeRESUMO
The Transcription factor BarH like homeobox 1 (BARHL1) is overexpressed in medulloblastoma and plays a role in neurogenesis. However, much about the BARHL1 regulatory networks and their functions in neurodegenerative and neoplastic disorders is not yet known. In this study, using a tissue microarray (TMA), we report for the first time that BARHL1 is downregulated in hormone-negative breast cancers and Alzheimer's disease (AD). Furthermore, using an integrative bioinformatics approach and mining knockout mouse data, we show that: (i) BARHL1 and Estrogen Receptor 1 (ESR1) may constitute a network that regulates Neurotrophin 3 (NTF3)- and Brain Derived Neurotrophic Factor (BDNF)-mediated neurogenesis and neural survival; (ii) this is probably linked to AD pathways affecting aberrant post-translational modifications including SUMOylation and ubiquitination; (iii) the BARHL1-ESR1 network possibly regulates ß-amyloid metabolism and memory; and (iv) hsa-mir-18a, having common key targets in the BARHL1-ESR1 network and AD pathway, may modulate neuron death, reduce ß-amyloid processing and might also be involved in hearing and cognitive decline associated with AD. We have also hypothesized why estrogen replacement therapy improves AD condition. In addition, we have provided a feasible new mechanism to explain the abnormal function of mossy fibers and cerebellar granule cells related to memory and cognitive decline in AD apart from the Tau and amyloid pathogenesis through our BARHL1-ESR1 axis.
RESUMO
INTRODUCTION: Most prognostic studies in differentiated carcinoma have included a high number of papillary carcinomas and few follicular carcinomas, and not all of their conclusions therefore apply to the latter. OBJECTIVE: To analyze the prognostic factors of follicular thyroid carcinoma. SELECTION CRITERIA: Patients with histological diagnosis of follicular carcinoma who had undergone potentially curative surgery, had no disseminated disease at diagnosis, and had been followed up for at least 5 years. STUDY VARIABLES: Tumor recurrence was defined as: 1) tumor lesions with cytological analysis suggesting malignancy and/or 2) patients with total thyroidectomy with thyroglobulin levels >2 ng/mL. Clinical, therapeutic, and histological parameters were analyzed to assess prognostic factors. RESULTS: Recurrence was found in 25 (38%) of the 66 study patients during a follow-up period of 99 ± 38 months. Most patients with recurrence (n=20) had increased Tg levels without anatomical location, and were initially treated with radioactive I131. In the remaining 5 cases, surgical excision of the lesion was performed, and three patients required surgery during the follow-up period. Two patients died due to the disease (3%), and two other patients (3%) currently have distant metastases. Mean disease-free interval was 154 ± 14 months, and rates of disease-free patients at 5, 10, 15, and 20 years were 71, 58, 58, and 58% respectively. Clinical factors influencing recurrence included 1) age (p=0.0035); 2) sex (p=0.0114); and 3) cervical pain (p=0.0026). Histological/surgical factors associated with recurrence included 1) infiltration into neighboring structures (p=0.0000); 2) type of carcinoma (p=0.0000); 3) size (p=0.0162); 4) vascular invasion (p=0.0085); and 5) adenopathies (p=0.046). In the multivariate study, cervical pain (p=0.018) and extrathyroid invasion (p=0.045) continued to be significant factors. CONCLUSIONS: In follicular carcinoma, rates of disease-free patients are 71% at 5 years and 58% at 10 years, and the main predictive factors are presence of local clinical symptoms and infiltration into neighboring structures.
Assuntos
Adenocarcinoma Folicular/terapia , Recidiva Local de Neoplasia/diagnóstico , Neoplasias da Glândula Tireoide/terapia , Adenocarcinoma Folicular/patologia , Adenocarcinoma Folicular/radioterapia , Adenocarcinoma Folicular/cirurgia , Adulto , Fatores Etários , Intervalo Livre de Doença , Feminino , Seguimentos , Humanos , Radioisótopos do Iodo/uso terapêutico , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Recidiva Local de Neoplasia/sangue , Prognóstico , Compostos Radiofarmacêuticos/uso terapêutico , Estudos Retrospectivos , Fatores Sexuais , Tireoglobulina/sangue , Neoplasias da Glândula Tireoide/patologia , Neoplasias da Glândula Tireoide/radioterapia , Neoplasias da Glândula Tireoide/cirurgia , Tireoidectomia , Adulto JovemAssuntos
Mama/irrigação sanguínea , Mama/patologia , Linfangioma/patologia , Sistema Linfático/anormalidades , Adulto , Biópsia com Agulha de Grande Calibre/métodos , Mama/diagnóstico por imagem , Diagnóstico Diferencial , Feminino , Humanos , Linfangioma/cirurgia , Sistema Linfático/patologia , Imageamento por Ressonância Magnética/métodos , Mamografia/métodos , Mastectomia Segmentar/métodos , Resultado do TratamentoRESUMO
No disponible
Assuntos
Humanos , Feminino , Adulto , Adenomioepitelioma/patologia , Adenomioepitelioma/cirurgia , Neoplasias da Mama/patologia , Neoplasias da Mama/cirurgia , Imageamento por Ressonância Magnética/métodos , Mamografia/métodos , Mastectomia Segmentar/métodos , Diagnóstico Diferencial , Erros de Diagnóstico/prevenção & controle , Mama/diagnóstico por imagem , Mama/cirurgiaRESUMO
Crohn's disease is one of the causes of secondary amyloidosis, which can lead to amyloid infiltration of the thyroid gland. It is essential to follow strict controls to prevent the appearance of a large amyloid goiter. Two patients with amyloid goiter secondary to Crohn's disease, with a large adipose tissue component and who required surgical treatment, were studied. Both surgical interventions were difficult because of the fragility of the thyroid tissue. A patient with Crohn's disease and secondary amyloidosis could begin to develop amyloid goiter. This is usually fast growing and commonly causes compressive symptoms, although in some cases it only grows in the neck with no evidence of these symptoms. When surgery is indicated, patients should be remitted to hospitals with experienced endocrine surgeons, given that there is a high risk of developing complications.
Assuntos
Amiloidose/etiologia , Doença de Crohn/complicações , Bócio/etiologia , Glândula Tireoide/patologia , Adulto , Amiloide/metabolismo , Amiloidose/metabolismo , Amiloidose/patologia , Doença de Crohn/metabolismo , Doença de Crohn/patologia , Feminino , Bócio/metabolismo , Bócio/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Glândula Tireoide/metabolismo , Tireoidectomia , Resultado do TratamentoRESUMO
No disponible
Assuntos
Humanos , Feminino , Pessoa de Meia-Idade , Leiomiossarcoma/cirurgia , Neoplasias Hepáticas/cirurgia , Laparoscopia/métodos , Resultado do Tratamento , Leiomiossarcoma/patologiaRESUMO
BACKGROUND AND AIM: Breast cancer in males is an uncommon tumor whose management is extrapolated from that used in female breast cancer. This study compared the histopathological and immunohistochemical features of symptomatic breast cancers in males and females. PATIENTS AND METHODS: A comparison was made between variables of breast cancers from 58 males and 155 females. A descriptive study, a bivariate analysis, and a multivariate analysis using logistic regression were performed. RESULTS: No differences were found in staging. Significant differences were seen in age (p<0.0005), proportion of papillary carcinoma (p=0.038) and proportion of tumors with an associated intraductal component (p=0.002). There was a greater proportion of males expressing estrogen (p=0.038) and progesterone (p<0.0005) receptors in their tumors, with a significantly higher proliferation index (p<0.0005). CONCLUSIONS: Breast cancer in males should be considered a condition biologically different from female breast cancer as a result of factors related to the different hormonal influences, reflected mainly in immunohistochemical differences.
Assuntos
Neoplasias da Mama Masculina/metabolismo , Neoplasias da Mama Masculina/patologia , Neoplasias Hormônio-Dependentes/metabolismo , Neoplasias Hormônio-Dependentes/patologia , Adulto , Idoso , Proliferação de Células , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Receptores de Progesterona/metabolismoRESUMO
INTRODUCCIÓN: La mayoría de los estudios pronósticos en el carcinoma diferenciado incluyen un alto número de carcinomas papilares y pocos foliculares, por lo que no todas sus conclusiones son aplicables a este último. OBJETIVO: Analizar los factores pronósticos, tanto clínicos, histológicos como terapéuticos, del carcinoma folicular de tiroides. PACIENTES Y MÉTODOS: Criterios de selección: pacientes con el diagnóstico histológico de carcinoma folicular, sin enfermedad diseminada al diagnóstico, con cirugía potencialmente curativa, y con un seguimiento mínimo de 5 años. Variables de estudio: se consideró recidiva del tumor: a) lesiones tumorales con citología sospechosa de malignidad; y/o b) el aumento de los niveles de tiroglobulina mayor de 2 ng/ml en pacientes con tiroidectomía total. Para valorar los factores pronósticos se analizan variables clínicas, terapéuticas e histológicas. Estadística: curvas de supervivencia aplicando el test de Breslow. Modelo de regresión de Cox. RESULTADOS: Se han presentado 25 recidivas (38%) en los 66 pacientes estudiados. La mayoría eran recidivas analíticas (n=20) que fueron tratadas con I-131. En los casos restantes (n=5) se realizó exéresis de la lesión localizada y posteriormente se aplicó I131. Actualmente, dos casos (3%) presentan metástasis a distancia, y otros dos (3%) han sido éxitus por evolución de la enfermedad. El tiempo medio libre de enfermedad fue de 154 ± 14 meses, siendo las tasas de pacientes libres de enfermedad a los 5, 10, 15 y 20 años del 71, 58, 58 y 58% respectivamente. Los factores que influyen en la recidiva son: 1) la edad (p = 0,0035); 2) el sexo (p = 0,0114); 3) la clínica local (p = 0,0026); 4) la infiltración de estructuras vecinas (p = 0,0000); 5) el tipo de carcinoma (p = 0,0000); 6) el tamaño (p = 0,0162); 7) la invasión vascular (p = 0,0085); y 8) las adenopatías (p = 0,046). En el estudio multivariante persisten la clínica local (p = 0,018) y la infiltración de estructuras (p = 0,045). CONCLUSIONES: En el carcinoma folicular los principales factores predictivos son la presencia de clínica local al diagnóstico y la infiltración de estructuras vecinas
INTRODUCTION: Most prognostic studies in differentiated carcinoma have included a high number of papillary carcinomas and few follicular carcinomas, and not all of their conclusions therefore apply to the latter. OBJECTIVE: To analyze the prognostic factors of follicular thyroid carcinoma. PATIENTS AND METHODS: Selection criteria: Patients with histological diagnosis of follicular carcinoma who had undergone potentially curative surgery, had no disseminated disease at diagnosis, and had been followed up for at least 5 years. Study Variables: Tumor recurrence was defined as: 1) tumor lesions with cytological analysis suggesting malignancy and/or 2) patients with total thyroidectomy with thyroglobulin levels >2 ng/mL. Clinical, therapeutic, and histological parameters were analyzed to assess prognostic factors. RESULTS: Recurrence was found in 25 (38%) of the 66 study patients during a follow-up period of 99 ± 38 months. Most patients with recurrence (n=20) had increased Tg levels without anatomical location, and were initially treated with radioactive I131. In the remaining 5 cases, surgical excision of the lesion was performed, and three patients required surgery during the follow-up period. Two patients died due to the disease (3%), and two other patients (3%) currently have distant metastases. Mean disease-free interval was 154 ± 14 months, and rates of disease-free patients at 5, 10, 15, and 20 years were 71, 58, 58, and 58% respectively. Clinical factors influencing recurrence included 1) age (p = 0.0035); 2) sex (p = 0.0114); and 3) cervical pain (p = 0.0026). Histological/surgical factors associated with recurrence included 1) infiltration into neighboring structures (p = 0.0000); 2) type of carcinoma (p = 0.0000); 3) size (p = 0.0162); 4) vascular invasion (p = 0.0085); and 5) adenopathies (p = 0.046). In the multivariate study, cervical pain (p = 0.018) and extrathyroid invasion (p = 0.045) continued to be significant factors. CONCLUSIONS: In follicular carcinoma, rates of disease-free patients are 71% at 5 years and 58% at 10 years, and the main predictive factors are presence of local clinical symptoms and infiltration into neighboring structures
Assuntos
Humanos , Carcinoma Papilar, Variante Folicular/patologia , Neoplasias da Glândula Tireoide/patologia , Invasividade Neoplásica/patologia , Prognóstico , Antineoplásicos/uso terapêutico , TireoidectomiaRESUMO
La esclerosis hepatoportal se caracteriza por hipertensión portal intrahepática presinusoidal asociada a esplenomegalia y anemia en pacientes con un hígado no cirrótico. La biopsia hepática es fundamental, sobre todo para descartar otros procesos. Se trata de un cuadro de etiología desconocida cuya gran mayoría de los casos se ha descrito en países orientales, si bien podría estar infradiagnosticada en Occidente. Se manifiesta con síntomas asociados a la hipertensión portal y el espectro clínico es muy amplio: desde anemia con pruebas de función hepática normales hasta hemorragia por varices esofagogástricas. Su tratamiento es el de las complicaciones y el pronóstico es mejor que en los pacientes con cirrosis. Presentamos tres casos de EHP que presentan estadios clínicos diferentes, así como los hallazgos de las biopsias hepáticas, su evolución clínica posterior y una revisión de la literatura científica(AU)
Hepatoportal sclerosis (HPS) is characterized by presinusoidal intrahepatic portal hypertension associated with splenomegaly and anemia in patients with non-cirrhotic liver. Liver biopsy is essential, especially to rule out other processes. Being a disease of unknown etiology, the majority of cases have been described in eastern countries. However, it may be an underdiagnosed disease in the West. Symptoms are related to portal hypertension and the clinical spectrum is wide, ranging from anemia with normal liver function tests to bleeding due to esophageal varices. Treatment is directed to the complications and the prognosis is better than in patients with cirrhosis. We report three cases of HPS presenting at different clinical stages and the findings of liver biopsies, the clinical outcomes and a review of scientific literature(AU)