RESUMO
Avoidance of steroids in pediatric liver transplantation may reduce toxicity and morbidity. The aim of this study was to analyze the feasibility of a steroid-free tacrolimus-basiliximab immunosuppression scheme, the risk factors associated with steroid requirement, and safety parameters. Patients who underwent liver transplantation for biliary atresia between 2011 and 2019 were included and followed for 6 months after transplantation. Immunosuppression consisted of tacrolimus-based treatment with basiliximab induction. Steroid-free survival was estimated, and risk factors for steroid requirement were evaluated using multivariate Cox regression analysis. A total of 76 patients were included, of whom 42 (55.3%) required steroids (>14 d) due to biopsy-proven acute rejection (47.6%, n = 20), instability in liver function tests (35.7%, n = 15), tacrolimus-related adverse drug reactions (14.3%, n = 6), or other reasons (bronchospasm episode, n = 1). Steroid-free survival was 45.9% (95% CI, 35.9-58.8). Independent factors associated with steroid requirement included tortuosity in tacrolimus trough levels (≥1.76 vs. <1.76: HR 5.8, 95% CI, 2.6-12.7; p < 0.001) and mean tacrolimus trough levels (≥ 6.4 ng/mL vs. < 6.4 ng/mL: HR 0.4, 95% CI, 0.2-0.7; p = 0.002). The rate of bacterial and viral infections was comparable between patients with and without steroids, although in the former group, cytomegalovirus infection developed earlier ( p = 0.03). Patients receiving steroids had higher total cholesterol, LDL, and HDL levels ( p < 0.05) during follow-up, but no changes in the height Z-score were observed 1 year after transplantation. Basiliximab induction in combination with tacrolimus-based treatment avoided steroid requirements in 45% of the patients. Tacrolimus variability and trough levels below 6.4 ng/mL independently increased the risk of steroid requirement. Further efforts should be focused on personalizing immunosuppressive treatment.
Assuntos
Transplante de Fígado , Tacrolimo , Humanos , Criança , Basiliximab/efeitos adversos , Tacrolimo/efeitos adversos , Transplante de Fígado/efeitos adversos , Anticorpos Monoclonais/efeitos adversos , Estudos de Viabilidade , Imunossupressores/efeitos adversos , Terapia de Imunossupressão/efeitos adversos , Esteroides/efeitos adversos , Rejeição de Enxerto/epidemiologia , Rejeição de Enxerto/prevenção & controle , Rejeição de Enxerto/tratamento farmacológicoRESUMO
BACKGROUND: Information on the epidemiology of pediatric liver tumors in Latin America is limited. PURPOSE: To describe the incidence of liver tumors in a pediatric registry in Argentina according to geographic region, national trends over 16 years, and survival related to stage, age, sex, and care center. METHODS: Newly diagnosed liver tumors cases are registered in the Argentine Pediatric Oncology Hospital Registry (ROHA) with an estimated coverage of 91% of national cases. Age-standardized incidence rate per millon (ASR) was calculated based on the National Vital Statistics Reports. Five-year overall survival (OS) was estimated using the Kaplan-Meier method. The log-rank test was used to compare subgroup survival. RESULTS: Two hundred seven cases of hepatoblastoma (HB) and 73 of hepatocellular carcinoma (HCC) were identified. ASR of liver tumors was 1.8/million (95% confidence Interval [CI], 1.6-2.0) per year. ASR was 1.4 (1.2-1.6) for HB and 0.4 (0.3-0.5) for HCC. For HB, the highest incidence was found in the northwest region including the Altiplano. OS was 60.4% (53.4-66.8) for HB and 36.1% (25.2-47.2) for HCC. Five-year survival rate of children with metastatic HB treated at liver transplant hospitals (LTH) was 54.2% (30.3-73.0) compared to 13.3% (2.2-34.6) for those seen at other hospitals (OH) (P = .02), while for HCC this rate was 46.3% (30.7-60.6) at LTH compared to 17.5% (3.1-41.9) at OH (P = .01). CONCLUSIONS: The incidence rate of pediatric liver tumors was stable over the 16-year study period. Patients may benefit if at treatment initiation they are evaluated jointly with LTH specialists to define treatment strategies.
Assuntos
Institutos de Câncer/estatística & dados numéricos , Carcinoma Hepatocelular/epidemiologia , Carcinoma Hepatocelular/mortalidade , Neoplasias Hepáticas/epidemiologia , Neoplasias Hepáticas/mortalidade , Mortalidade/tendências , Sistema de Registros/estatística & dados numéricos , Adolescente , Argentina/epidemiologia , Carcinoma Hepatocelular/terapia , Criança , Pré-Escolar , Terapia Combinada , Feminino , Seguimentos , Humanos , Incidência , Lactente , Recém-Nascido , Neoplasias Hepáticas/terapia , Masculino , Prognóstico , Taxa de SobrevidaRESUMO
BACKGROUND: A limited number of publications correlate bidimensional shear-wave elastography (2-D SWE) and stages of liver fibrosis in children. OBJECTIVE: To correlate liver elastography values using 2-D SWE and liver biopsy classified by Knodell-Ishak score to evaluate fibrosis in pediatric patients with liver disease, and to propose values of 2-D SWE (kPa) correlating with Knodell-Ishak score, which have not been defined in the literature. MATERIALS AND METHODS: We conducted a prospective cross-sectional observational study on the performance of diagnostic tests. Between June 2016 and June 2018, elastography was performed in 213 children and young adults who had undergone liver biopsy. B mode, Doppler and 2-D SWE were performed using an Aixplorer (SuperSonic Imagine, Aix-en-Provence, France). Histology samples were classified using the Knodell-Ishak score. We evaluated performance by assessing sensitivity, specificity, positive predictive value and negative predictive value. To determine cut-off points for the continuous variables, we used receiver operating characteristic (ROC) curves. All the cutoff values we established apply only to the SuperSonic Aixplorer system. RESULTS: Measurement with 2-D SWE was successful, with a good correlation with fibrosis stage. The area under the curve (AUC) to differentiate between early (Stages 1-2) and moderate (Stages 3-4) fibrosis was 0.91 (95% confidence interval [CI]: 0.87-0.96), with a sensitivity of 92% and specificity of 86%, with a cutoff value 12 kPa (2 m/s). The AUC of severe fibrosis (early stages of cirrhosis; Stage 5) was 0.95 (95% CI: 0.92-0.97), with a sensitivity of 94% and specificity of 90%, with a cutoff value 18.5 kPa (2.48 m/s). In two patients with hematopoietic stem cell transplantation and suspicion of graft versus host disease we found high 2-D SWE values in correlation with the fibrosis stages (Stage 0 with a median of 13 kPa [2.08 m/s] with hemosiderosis Grade 2 in one child and Stage 2 with a median of 46 kPa [3.91 m/s] and hemosiderosis Grade 4 in the other). CONCLUSION: Our study shows the usefulness and accuracy of 2-D SWE for detecting liver fibrosis in pediatric patients. We propose reference values for Knodell-Ishak Stages 1 and 5. We found hemosiderosis as a possible confounding factor that hasn't been described with 2-D SWE.
Assuntos
Técnicas de Imagem por Elasticidade , Cirrose Hepática/diagnóstico por imagem , Cirrose Hepática/patologia , Adolescente , Biópsia , Criança , Pré-Escolar , Estudos Transversais , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Estudos Prospectivos , Valores de Referência , Sensibilidade e EspecificidadeRESUMO
Tacrolimus is the cornerstone in pediatric liver transplant immunosuppression. Despite close monitoring, fluctuations in tacrolimus blood levels affect safety and efficacy of immunosuppressive treatments. Identifying the factors related to the variability in tacrolimus exposure may be helpful in tailoring the dose. The aim of the present study was to characterize the clinical, pharmacological, and genetic variables associated with systemic tacrolimus exposure in pediatric liver transplant patients. De novo transplant patients with a survival of more than 1 month were considered for inclusion and were genotyped for cytochrome P450 3A5 (CYP3A5). Peritransplant clinical factors and laboratory covariates were recorded retrospectively between 1 month and 2 years after transplant, including alanine aminotransferase (ALT), aspartate aminotransferase, hematocrit, and tacrolimus predose steady-state blood concentrations collected 12 hours after tacrolimus dosing. A linear mixed effect (LME) model was used to assess the association of these factors and the log-transformed tacrolimus dose-normalized trough concentration (logC0/D) levels. Bootstrapping was used to internally validate the final model. External validation was performed in an independent group of patients who matched the original population. The developed LME model described that logC0/D increases with increases in time after transplant (ß = 0.019, 95% confidence interval [CI], 0.010-0.028) and ALT values (ß = 0.00030, 95% CI, 0.00002-0.00056), whereas logC0/D is significantly lower in graft CYP3A5 expressers compared with nonexpressers (ß = -0.349, 95% CI, -0.631 to -0.062). In conclusion, donor CYP3A5 genotype, time after transplant, and ALT values are associated with tacrolimus disposition between 1 month and 2 years after transplant. A better understanding of tacrolimus exposure is essential to minimize the occurrence of an out-of-range therapeutic window that may lead to adverse drug reactions or acute rejection.
Assuntos
Citocromo P-450 CYP3A/genética , Rejeição de Enxerto/prevenção & controle , Imunossupressores/farmacocinética , Transplante de Fígado/efeitos adversos , Tacrolimo/farmacocinética , Administração Oral , Adolescente , Adulto , Alanina Transaminase/sangue , Alanina Transaminase/metabolismo , Aloenxertos/metabolismo , Argentina , Aspartato Aminotransferases/sangue , Aspartato Aminotransferases/metabolismo , Criança , Monitoramento de Medicamentos/métodos , Doença Hepática Terminal/sangue , Doença Hepática Terminal/cirurgia , Feminino , Seguimentos , Rejeição de Enxerto/sangue , Rejeição de Enxerto/imunologia , Humanos , Imunossupressores/administração & dosagem , Imunossupressores/efeitos adversos , Fígado/metabolismo , Masculino , Pessoa de Meia-Idade , Modelos Biológicos , Polimorfismo Genético , Estudos Retrospectivos , Tacrolimo/administração & dosagem , Tacrolimo/efeitos adversos , Fatores de TempoRESUMO
BACKGROUND: Despite advances in surgical procedures and the optimization of immunosuppressive therapies in pediatric liver transplantation, acute rejection (AR) and serious adverse drug reaction (ADR) to tacrolimus still contribute to morbidity and mortality. Identifying risk factors of safety and efficacy parameters may help in optimizing individual immunosuppressive therapies. This study aimed to identify peritransplant predictors of AR and factors related to the risk of ADR to tacrolimus in a large Latin American cohort of pediatric liver transplant patients. METHODS: We performed a retrospective cohort study in a pediatric liver transplant population (n = 72). Peritransplant variables were collected retrospectively including demographic, clinical, laboratory parameters, genomic (CYP3A5 donor and recipients polymorphism), and tacrolimus trough concentrations (C0) over a 2-year follow-up period. Variability in tacrolimus C0 was calculated using percent coefficient of variation and tortuosity. ADR- and AR-free survival rates were calculated using the Kaplan-Meier method, and risk factors were identified by multivariate Cox regression models. RESULTS: Cox-proportional hazard models identified that high tortuosity in tacrolimus C0 was associated with an 80% increased risk of AR [hazard ratio (HR), 1.80; 95% confidence interval (CI), 1.01-3.22; P < 0.05], whereas steroid in maintenance doses decreased this risk (HR, 0.56; 95% CI, 0.31-0.99; P < 0.05). Forty-six patients experienced at least one ADR including hypomagnesemia, nephrotoxicity, hypertension, malignancies, and tremor as a first event. Multivariate analysis showed that C0 values 10 days before the event (HR, 1.25; 95% CI, 1.21-1.39; P < 0.0001) and CYP3A5 expresser recipients (HR, 2.05; 95% CI, 1.03-4.06; P < 0.05) were independent predictors of ADR. CONCLUSIONS: Tacrolimus C0 values, its variability, and CYP3A5 polymorphisms were identified as risk factors of AR and tacrolimus ADR. This knowledge may help to control and reduce their incidence in pediatric liver transplant patients. Prospective studies are important to validate these results.
Assuntos
Rejeição de Enxerto/epidemiologia , Transplante de Fígado/estatística & dados numéricos , Tacrolimo/efeitos adversos , Argentina/epidemiologia , Pré-Escolar , Citocromo P-450 CYP3A/genética , Feminino , Genótipo , Humanos , Imunossupressores/efeitos adversos , Imunossupressores/sangue , Estimativa de Kaplan-Meier , Masculino , Polimorfismo Genético/genética , Estudos Retrospectivos , Fatores de Risco , Tacrolimo/sangueRESUMO
Patients with retinoblastoma and central nervous system (CNS) involvement are rarely curable with available treatments. We designed a high-dose intra-arterial regimen targeting the ophthalmic artery and chiasm combined with intrathecal chemotherapy to treat a 4-year-old patient with retinoblastoma metastasized to the CNS. After three cycles of this regimen, including carboplatin, melphalan, and intrathecal topotecan, a partial response of the orbital tumor mass and chiasmatic lesion, and complete response in the cerebrospinal fluid and bone marrow were achieved. This new treatment strategy may be explored as a treatment component for patients with overt extraocular retinoblastoma and CNS dissemination.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Neoplasias da Retina/tratamento farmacológico , Retinoblastoma/tratamento farmacológico , Carboplatina/administração & dosagem , Neoplasias do Sistema Nervoso Central/tratamento farmacológico , Neoplasias do Sistema Nervoso Central/secundário , Pré-Escolar , Humanos , Infusões Intra-Arteriais , Injeções Espinhais , Masculino , Melfalan/administração & dosagem , Neoplasias da Retina/patologia , Retinoblastoma/secundário , Topotecan/administração & dosagemRESUMO
High levels of circulating EBV load are used as a marker of post-transplant lymphoproliferative disorders (PTLD). There is no consensus regarding the threshold level indicative of an increase in peripheral EBV DNA. The aim of the study was to clinically validate a developed EBV quantification assay for early PTLD detection. Transversal study: paired peripheral blood mononuclear cells (PBMC), plasma and oropharyngeal lymphoid tissue (OLT) from children undergoing a solid organ transplant with (n=58) and without (n=47) PTLD. Retrospective follow-up: 71 paired PBMC and plasma from recipients with (n=6) and without (n=6) PTLD history. EBV load was determined by real-time PCR. The diagnostic ability to detect all PTLD (categories 1-4), advanced PTLD (categories 2-4) or neoplastic PTLD (categories 3 and 4) was estimated by analyzing the test performance at different cut-off values or with a load variation greater than 0.5log units. The higher diagnostic performance for identifying all, advanced or neoplastic PTLD, was achieved with cut-off values of 1.08; 1.60 and 2.47log EBVgEq/10(5) PBMC or 2.30; 2.60; 4.47loggEq/10(5) OLT cells, respectively. EBV DNA detection in plasma showed high specificity but low (all categories) or high (advanced/neoplastic categories) sensitivity for PTLD identification. Diagnostic performance was greater when: (1) a load variation in PBMC or plasma was identified; (2) combining the measure of EBV load in PBMC and plasma. The best diagnostic ability to identify early PTLD stages was achieved by monitoring EBV load in PBMC and plasma simultaneously; an algorithm was proposed.
Assuntos
Infecções por Vírus Epstein-Barr/virologia , Transplante de Coração , Herpesvirus Humano 4/isolamento & purificação , Transplante de Rim , Transplante de Fígado , Transtornos Linfoproliferativos/virologia , Complicações Pós-Operatórias/virologia , Viremia/diagnóstico , Criança , Pré-Escolar , Estudos Transversais , DNA Viral/sangue , Detecção Precoce de Câncer , Infecções por Vírus Epstein-Barr/diagnóstico , Seguimentos , Humanos , Hospedeiro Imunocomprometido , Lactente , Leucócitos Mononucleares/virologia , Tecido Linfoide/virologia , Linfoma/diagnóstico , Linfoma/etiologia , Linfoma/virologia , Transtornos Linfoproliferativos/diagnóstico , Transtornos Linfoproliferativos/etiologia , Complicações Pós-Operatórias/diagnóstico , Complicações Pós-Operatórias/etiologia , Reação em Cadeia da Polimerase em Tempo Real , Estudos Retrospectivos , Carga ViralRESUMO
Tufting enteropathy (TE), previously known as intestinal epithelial dysplasia, is a rare congenital enteropathy characterized by refractory diarrhea in the neonatal period. It presents clinical and histological heterogeneity and may be associated with birth defects and punctuate keratitis. The causative gene(s) have not yet been identfied making prenatal diagnosis unavailable. Although there are milder phenotypes most require parenteral nutrition for prolonged periods with the risk of complications. TE becomes an indication for intestinal transplantation. We report the case of a 4-month-old male, born full term with a normal weight. The parents consulted because of severe malnutrition and chronic watery diarrhea. Duodenal and rectal biopsy was negative. Because of poor tolerance gastroclysis was changed to parenteral nutrition. The infant had several catheter-related infections and died at 13 months from catheter-associated complications. Histopathological autopsy was performed. The material was fixed in paraffin and studied with routine techniques. PAS and immunohistochemistry for CD10 were performed. We observed villous atrophy with intestinal epithelial dysplasia and disorganization on the surface of epithelial cells resembling tufts in jejunal and ileal tissue. The objective of this study was to present a rare case of neonatal enteropathy, especially TE, describe the methodology used to study the biopsy, and discuss the differential diagnoses. TE is a rare neonatal enteropathy that is difficult to diagnose and manage. Children in whom TE is suspected should be referred to specialized pediatric centers, with the option of intestinal transplantation.
Assuntos
Diarreia Infantil/patologia , Síndromes de Malabsorção/patologia , Diagnóstico Diferencial , Diarreia Infantil/cirurgia , Evolução Fatal , Humanos , Lactente , Síndromes de Malabsorção/cirurgia , MasculinoRESUMO
Tumors of the sexual and stromal cords are rare neoplasms, corresponding to 8 % of primary ovarian tumors. The tumor of the sexual cords with annular tubules of the ovary is considered a subtype and is uncommon. It can occur sporadically or associated with Peutz-Jeghers Syndrome, having different behavior and characteristics in each situation. We present the case of an adolescent patient with a diagnosis of a tumor of the sexual cords with annular tubules of the ovary associated with Peutz-Jeghers Syndrome.
Los tumores de los cordones sexuales y estromales son neoplasias poco frecuentes, que corresponden al 8 % de los tumores primarios del ovario. El tumor de los cordones sexuales con túbulos anulares del ovario es considerado un subtipo y es infrecuente. Puede presentarse de manera esporádica o asociado al síndrome de Peutz-Jeghers y tiene diferente comportamiento y características en cada situación. Se presenta el caso de una paciente adolescente con diagnóstico de tumor de los cordones sexuales con túbulos anulares del ovario asociado a síndrome de Peutz-Jeghers.
Assuntos
Neoplasias Ovarianas/diagnóstico , Síndrome de Peutz-Jeghers/diagnóstico , Tumores do Estroma Gonadal e dos Cordões Sexuais/diagnóstico , Adolescente , Feminino , Humanos , Neoplasias Ovarianas/patologia , Síndrome de Peutz-Jeghers/patologia , Tumores do Estroma Gonadal e dos Cordões Sexuais/patologiaRESUMO
The evidence available in the pediatric population is limited for making clinical decisions regarding the optimization of tacrolimus (TAC) in pharmacotherapy. The objective of this study was to estimate the frequency of CYP3A5 genetic polymorphisms and their relationship with tacrolimus requirements in the pediatric population. This was a longitudinal cohort study with a two-year follow-up of 77 patients under 18 years old who underwent a liver transplant during the period 2009-2012 at the J.P. Garrahan Pediatric Hospital. Tacrolimus levels from day five up to two years after the transplant were obtained from hospital records of routine therapeutic drug monitoring. The genotyping of CYP3A5 (CYP3A5*1/*3 or *3/*3) was performed in liver biopsies from both the donor and the recipient. The frequency of CYP3A5*1 expression for recipients was 37.1% and 32.2% for donors. Patients who received an expresser organ showed lower Co/dose, especially following 90 days after the surgery. The role of each polymorphism is different according to the number of days after the transplant, and it must be taken into account to optimize the benefits of TAC therapy during the post-transplant induction and maintenance phases.
RESUMO
Tuberous sclerosis is an autosomal dominant disorder with a wide clinical spectrum of disease. It is characterized by development of benign tumors in multiple organs due to a disturbance in cellular growth and differentiation. It usually affects skin, brain, heart and kidney. Gastrointestinal involvement is rare and mainly restricted to adults and sigmoid colon and rectum. In children there are only two cases; our patient would be the third. We present a patient with tuberous sclerosis who began at the first month of life with repeated intestinal subocclusion. The videocolonoscopy showed a mass protruding into the lumen of the ascending colon. Right hemicolectomy was performed. The anatomopathological report corresponded to a hamartomatous polyp. The clinical and nutritional evolution in the postoperative period was very favorable. Although uncommon, the hamartomatous polyp should be considered in the differential diagnosis of intestinal occlusion in pediatrics.
La esclerosis tuberosa es una enfermedad autosómica dominante con gran variabilidad de expresión clínica. Se caracteriza por la presencia de tumores benignos en distintos órganos debidos a un desorden en la proliferación y diferenciación celular. Afecta, especialmente, la piel, el sistema nervioso central, el corazón y el riñón. El compromiso intestinal es infrecuente; afecta a adultos y compromete el colon sigmoide y el recto. En niños, hay solo dos casos descritos en la literatura; nuestra paciente sería el tercero. Presentamos a una paciente con esclerosis tuberosa, que comenzó, desde el mes de vida, con cuadros reiterados de suboclusión intestinal. La videocolonoscopía mostró una formación mamelonada que protruía hacia la luz del colon ascendente. Se realizó una hemicolectomía derecha. El informe anatomopatológico correspondió a un pólipo hamartomatoso. La evolución clínica y nutricional en el posquirúrgico fue muy favorable. Aunque poco frecuente, el pólipo hamartomatoso debe considerarse en el diagnóstico diferencial de oclusión intestinal en pediatría.
Assuntos
Doenças do Colo/etiologia , Obstrução Intestinal/etiologia , Esclerose Tuberosa/complicações , Doenças do Colo/complicações , Feminino , Hamartoma/complicações , Humanos , Recém-Nascido , Pólipos/complicaçõesAssuntos
Hepatite Autoimune/diagnóstico , Hepatite Autoimune/tratamento farmacológico , Poliendocrinopatias Autoimunes/tratamento farmacológico , Poliendocrinopatias Autoimunes/imunologia , Azatioprina/uso terapêutico , Pré-Escolar , Seguimentos , Doenças Genéticas Ligadas ao Cromossomo X/complicações , Doenças Genéticas Ligadas ao Cromossomo X/tratamento farmacológico , Doenças Genéticas Ligadas ao Cromossomo X/imunologia , Hepatite Autoimune/complicações , Humanos , Masculino , Poliendocrinopatias Autoimunes/complicações , Prednisona/uso terapêutico , Síndrome , Resultado do TratamentoRESUMO
Plasma cell neoplasia occurs as a result of the expansion of an immunoglobulin-secreting B-cells clones, known as monoclonal component or M component. Malignant neoplasias include multiple myeloma and Waldenstrom macroglobulinemia, while premalignant conditions comprise monoclonal gammopathies of unknown significance (MGUS). MGUS present a monoclonal component with no signs of multiple myeloma, Waldenström macroglobulinemia, primary amyloidosis or other disorders. Pathological, radiological and clinical features are required for the diagnosis. Approximately 25% of patients with MGUS will become multiple myeloma, primary amiloidosis, macroglobulinemia, or other lymphoproliferative disease, which would be a premyelomatous condition. The objective of this study was to determine the clinical implications of immunophenotyping by flow cytometry and of the detection of clonality by molecular biology. A total of 32 patients were studied. Seven of them were diagnosed with multiple myeloma, and 25 with monoclonal gammopathy under study. These 32 patients were divided into four groups, based on their clinical data and flow cytometry outcome. In patients with non-diagnostic flow cytometry detection of immunoglobulin heavy chain gene rearrangements by PCR was performed, and monoclonality was found in 59% of the cases. The study of immunoglobulin heavy chain gene rearrangements by molecular biology allows a more sensitive detection of clonality.
Assuntos
Rearranjo Gênico de Cadeia Pesada de Linfócito B/genética , Imunofenotipagem/métodos , Mieloma Múltiplo/genética , Paraproteinemias/genética , Idoso , Idoso de 80 Anos ou mais , Medula Óssea/patologia , Feminino , Citometria de Fluxo/métodos , Humanos , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/patologia , Paraproteinemias/patologia , Reação em Cadeia da Polimerase , Sensibilidade e EspecificidadeRESUMO
Malignant tumors of the larynx are very rare in children. They are often diagnosed late, since the initial symptoms are attributed to the process of larynx development or to other, more common pediatric diseases. Early visualization of the larynx with the aid of flexible or rigid fiberoptic laryngoscopy is essential in children having symptoms suggestive of laryngeal disease. Laryngeal lymphoma in children is exceptionally unusual. The certainty of the diagnosis, which is often very difficult to achieve, is generally confirmed by a tissue biopsy. In the present work, we describe the case of a non-Hodgkin lymphoblastic T-cell lymphoma of the larynx in an eight-year-old boy.
Assuntos
Neoplasias Laríngeas/patologia , Laringe/patologia , Linfoma de Células T/patologia , Biópsia , Criança , Humanos , Neoplasias Laríngeas/tratamento farmacológico , Laringoscopia , Linfoma de Células T/tratamento farmacológico , MasculinoRESUMO
Los tumores de los cordones sexuales y estromales son neoplasias poco frecuentes, que corresponden al 8 % de los tumores primarios del ovario. El tumor de los cordones sexuales con túbulos anulares del ovario es considerado un subtipo y es infrecuente. Puede presentarse de manera esporádica o asociado al síndrome de Peutz-Jeghers y tiene diferente comportamiento y características en cada situación.Se presenta el caso de una paciente adolescente con diagnóstico de tumor de los cordones sexuales con túbulos anulares del ovario asociado a síndrome de Peutz-Jeghers
Tumors of the sexual and stromal cords are rare neoplasms, corresponding to 8 % of primary ovarian tumors. The tumor of the sexual cords with annular tubules of the ovary is considered a subtype and is uncommon. It can occur sporadically or associated with Peutz-Jeghers Syndrome, having different behavior and characteristics in each situation.We present the case of an adolescent patient with a diagnosis of a tumor of the sexual cords with annular tubules of the ovary associated with Peutz-Jeghers Syndrome
Assuntos
Humanos , Feminino , Adolescente , Síndrome de Peutz-Jeghers , Tumores do Estroma Gonadal e dos Cordões Sexuais/diagnóstico , Ovário/patologia , Tumores do Estroma Gonadal e dos Cordões Sexuais/cirurgia , NeoplasiasRESUMO
IMPORTANCE: Different staging systems for extraocular retinoblastoma have been published, but to date they have not been validated in large cohorts. OBJECTIVE: To review 533 patients (and pathology slides) with retinoblastoma included in 4 protocols (January 1, 1988, to December 31, 2009) who received uniform treatment. DESIGN AND SETTING: Retrospective review in a hospital setting. A critical analysis for detecting inconsistencies and omissions was performed. PARTICIPANTS: Patients were reclassified according to the modified St Jude Children's Research Hospital staging system, Grabowski-Abramson staging system, International Retinoblastoma Staging System (IRSS), and American Joint Committee on Cancer TNM staging system. MAIN OUTCOME AND MEASURE: The main outcome measure was disease-free survival (DFS), considering only extraocular relapse as an event. RESULTS: In the IRSS and the St Jude system, higher stages correlated with poorer DFS. For intraocular disease, only the TNM system and the IRSS included pathological definitions, and all systems except for the IRSS included substages without differences in DFS. Omissions of factors significantly associated with lower DFS included scleral invasion by the TNM system and massive choroidal invasion by the Grabowski-Abramson system. The St Jude system omits postlaminar optic nerve involvement, but this omission did not correlate significantly with lower DFS because these patients received intensive therapy. No differences in DFS were observed among substages for metastatic disease except for the presence of central nervous system involvement. All staging systems had inconsistencies in definitions of extent of disease. No system provides guidelines for imaging. CONCLUSIONS AND RELEVANCE: Only the IRSS and the St Jude system allowed for grouping of patients with increasing risk of extraocular relapse. For lower stages, only the IRSS considers all unequivocal pathological prognostic factors. For higher stages, all systems had redundant information, resulting in an excess of substages.
Assuntos
Neoplasias da Medula Óssea/secundário , Neoplasias Encefálicas/secundário , Neoplasias do Nervo Óptico/secundário , Neoplasias da Retina/patologia , Retinoblastoma/secundário , Neoplasias da Medula Óssea/terapia , Neoplasias Encefálicas/terapia , Pré-Escolar , Intervalo Livre de Doença , Enucleação Ocular , Seguimentos , Humanos , Lactente , Terapia Neoadjuvante , Invasividade Neoplásica , Estadiamento de Neoplasias , Disco Óptico/patologia , Neoplasias do Nervo Óptico/terapia , Neoplasias da Retina/terapia , Retinoblastoma/terapia , Estudos Retrospectivos , Fatores de Risco , Resultado do TratamentoRESUMO
OBJECTIVES: To evaluate the outcome of children with different degrees of choroidal invasion, to compare different systems for grading the extent of choroidal invasion, and to assess the role of concomitant prelaminar optic nerve and anterior segment invasion as predictors of extraocular relapse. DESIGN: Retrospective analysis of children included in 4 prospective protocols (January 1, 1989, through June 31, 2010). Children with postlaminar optic nerve or scleral involvement and overt extraocular disease were excluded. Adjuvant chemotherapy was not scheduled. All slides were reviewed, and massive involvement was classified according to 3 definitions: (1) extending at least 3 mm in any dimension, (2) through the choroid's whole thickness, and (3) more than 50% of the thickness and/or more than 1 cluster. RESULTS: One hundred sixty-seven children (35 with massive invasion) were studied (136 did not receive adjuvant therapy). The probability of 5-year event-free survival was 98.1% and the probability of overall survival was 98.7% because 1 patient relapsed. Children with massive invasion had a significantly lower event-free survival probability (94.2%) compared with those with focal invasion (99.2%) (P = .04). However, no significant difference was found in overall survival probability (98.7% vs 99.2%; P = .29). No significant effect of other risk factors was found. CONCLUSIONS: Survival was excellent without adjuvant therapy, and no other factors correlated with survival. Children with massive invasion have a higher relapse rate but comparable survival to those with focal invasion provided that aggressive therapy for extraocular relapse is available with adequate safety conditions.
Assuntos
Neoplasias da Coroide/patologia , Neoplasias da Retina/patologia , Retinoblastoma/patologia , Adolescente , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Criança , Pré-Escolar , Neoplasias da Coroide/mortalidade , Neoplasias da Coroide/terapia , Intervalo Livre de Doença , Enucleação Ocular , Feminino , Seguimentos , Humanos , Lactente , Imageamento por Ressonância Magnética , Masculino , Gradação de Tumores , Invasividade Neoplásica , Neoplasias da Retina/mortalidade , Neoplasias da Retina/terapia , Retinoblastoma/mortalidade , Retinoblastoma/terapia , Estudos Retrospectivos , Fatores de Risco , Taxa de Sobrevida , Tomografia Computadorizada por Raios XRESUMO
La esclerosis tuberosa es una enfermedad autosómica dominante con gran variabilidad de expresión clínica. Se caracteriza por la presencia de tumores benignos en distintos órganos debidos a un desorden en la proliferación y diferenciación celular. Afecta, especialmente, la piel, el sistema nervioso central, el corazón y el riñón. El compromiso intestinal es infrecuente; afecta a adultos y compromete el colon sigmoide y el recto. En niños, hay solo dos casos descritos en la literatura; nuestra paciente sería el tercero. Presentamos a una paciente con esclerosis tuberosa, que comenzó, desde el mes de vida, con cuadros reiterados de suboclusión intestinal. La videocolonoscopía mostró una formación mamelonada que protruía hacia la luz del colon ascendente. Se realizó una hemicolectomía derecha. El informe anatomopatológico correspondió a un pólipo hamartomatoso. La evolución clínica y nutricional en el posquirúrgico fue muy favorable. Aunque poco frecuente, el pólipo hamartomatoso debe considerarse en el diagnóstico diferencial de oclusión intestinal en pediatría.
Tuberous sclerosis is an autosomal dominant disorder with a wide clinical spectrum of disease. It is characterized by development of benign tumors in multiple organs due to a disturbance in cellular growth and differentiation. It usually affects skin, brain, heart and kidney. Gastrointestinal involvement is rare and mainly restricted to adults and sigmoid colon and rectum. In children there are only two cases; our patient would be the third. We present a patient with tuberous sclerosis who began at the first month of life with repeated intestinal subocclusion. The videocolonoscopy showed a mass protruding into the lumen of the ascending colon. Right hemicolectomy was performed. The anatomopathological report corresponded to a hamartomatous polyp. The clinical and nutritional evolution in the postoperative period was very favorable. Although uncommon, the hamartomatous polyp should be considered in the differential diagnosis of intestinal occlusion in pediatrics.
Assuntos
Humanos , Feminino , Recém-Nascido , Esclerose Tuberosa/complicações , Doenças do Colo/etiologia , Obstrução Intestinal/etiologia , Pólipos/complicações , Doenças do Colo/complicações , Hamartoma/complicaçõesRESUMO
High levels of circulating EBV load are used as a marker of post-transplant lymphoproliferative disorders (PTLD). There is no consensus regarding the threshold level indicative of an increase in peripheral EBV DNA. The aim of the study was to clinically validate a developed EBV quantification assay for early PTLD detection. Transversal study: paired peripheral blood mononuclear cells (PBMC), plasma and oropharyngeal lymphoid tissue (OLT) from children undergoing a solid organ transplant with (n = 58) and without (n = 47) PTLD. Retrospective follow-up: 71 paired PBMC and plasma from recipients with (n = 6) and without (n = 6) PTLD history. EBV load was determined by real-time PCR. The diagnostic ability to detect all PTLD (categories 1-4), advanced PTLD (categories 2-4) or neoplastic PTLD (categories 3 and 4) was estimated by analyzing the test performance at different cut-off values or with a load variation greater than 0.5 log units. The higher diagnostic performance for identifying all, advanced or neoplastic PTLD, was achieved with cut-off values of 1.08; 1.60 and 2.47 log EBV gEq/10(5) PBMC or 2.30; 2.60; 4.47 log gEq/10(5) OLT cells, respectively. EBV DNA detection in plasma showed high specificity but low (all categories) or high (advanced/neoplastic categories) sensitivity for PTLD identification. Diagnostic performance was greater when: (1) a load variation in PBMC or plasma was identified; (2) combining the measure of EBV load in PBMC and plasma. The best diagnostic ability to identify early PTLD stages was achieved by monitoring EBV load in PBMC and plasma simultaneously; an algorithm was proposed.
La carga alta del virus Epstein-Barr se utiliza como un marcador de desórdenes linfoproliferativos postrasplante (post-transplant lymphoproliferative disorders [PTLD]). El objetivo de este estudio fue validar clínicamente un ensayo de cuantificación del virus Epstein-Barr para la detección temprana de PTLD. Se efectuó un estudio transversal en el que se analizaron muestras pareadas de células mononucleares periféricas (CMP), de plasma y de tejido linfoide orofaríngeo de niños con trasplante de órgano sólido, con PTLD (n = 58) y sin PTLD (n = 47). En el seguimiento retrospectivo se incluyeron 71 muestras pareadas de CMP y de plasma de trasplantados, con PTLD (n = 6) y sin PTLD (n = 6). La carga viral se determinó por PCR en tiempo real. Se estimó la capacidad diagnóstica para detectar PTLD (categorías: todas vs. avanzadas vs. neoplásicas) analizando diferentes valores de corte o una variación de carga mayor de 0,5 logaritmos. El mayor desempeño diagnóstico para identificar todos los PTLD, los avanzados y los neoplásicos, se obtuvo con valores de corte de 1,08; 1,60 y 2,47 log copias/10(5) en CMP y de 2,30; 2,60 y 4,48 log copias/10(5) en células de tejido linfoide orofaríngeo, respectivamente. La detección del ADN del virus Epstein-Barr en el plasma mostró una especificidad alta, pero una sensibilidad baja (todas las categorías) o alta (categorías avanzadas o neoplásicas) para identificar PTLD. Se observó el desempeño diagnóstico más alto en las siguientes condiciones: 1) al identificar una variación de carga en CMP o en plasma; 2) combinando la medición de la carga viral en CMP y en plasma. La mejor capacidad diagnóstica para identificar las etapas tempranas de los PTLD se logró mediante el seguimiento simultáneo de la carga viral en CMP y en plasma; se propone un algoritmo.
Assuntos
Criança , Pré-Escolar , Humanos , Lactente , Complicações Pós-Operatórias/virologia , Viremia/diagnóstico , Transplante de Coração , Transplante de Rim , Transplante de Fígado , Herpesvirus Humano 4/isolamento & purificação , Infecções por Vírus Epstein-Barr/virologia , Transtornos Linfoproliferativos/virologia , Complicações Pós-Operatórias/diagnóstico , Complicações Pós-Operatórias/etiologia , DNA Viral/sangue , Leucócitos Mononucleares/virologia , Estudos Transversais , Estudos Retrospectivos , Seguimentos , Hospedeiro Imunocomprometido , Carga Viral , Infecções por Vírus Epstein-Barr/diagnóstico , Detecção Precoce de Câncer , Reação em Cadeia da Polimerase em Tempo Real , Tecido Linfoide/virologia , Linfoma/diagnóstico , Linfoma/etiologia , Linfoma/virologia , Transtornos Linfoproliferativos/diagnóstico , Transtornos Linfoproliferativos/etiologiaRESUMO
Neonatal hemochromatosis is a rare clinical pathologic entity, defined by severe neonatal liver failure of intrauterine onset associated with intra-and extra- hepatic siderosis that spares reticuloendothelial system. It is the most frequently recognized cause of liver failure in neonates. The cause is unknown but it may develop secondary to abnormal fetoplacental iron handling or perinatal liver disease or be familial or as a consequence of gestational alloimmune disease. It's a syndrome with a common feature rather than a single pathologic entity, with maternal transmission and a high recurrence in the sibship. Death from multisystem organ failure usually occurs in the first few days or weeks of life. We report two newborn with neonatal hemochromatosis. The first died for multiorgan failure, despite aggressive support. The second underwent to liver transplantation. Since 1993, an antioxidant-chelator cocktail has been used in addition to standard supportive care, but this remains controversial. By 2002, a preliminary report suggested that treatment with weekly intravenous immunoglobulin during the later half of pregnancy, for woman whose most recent gestation was affected with proven NH. The diagnosis is suspected in the presence of severely impaired hepatic synthetic function accompanied by high serum ferritin levels, but is confirmed only by demonstration of increased hepatic iron stores, and extra-hepatic siderosis shown by autopsy or in vivo, which can be achieved by biopsy of the minor salivary glands or magnetic resonance imaging. Neonatal hemochromatosis is the most common specific indication for liver transplantation in the first three months of life and appears to be the treatment of choice, and must as well be considered as soon as it becomes apparent that medical support, which should include chelation-antioxidant treatment, is ineffective, before irreversible neurological complications appear.