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1.
Medicina (B.Aires) ; 81(1): 91-95, mar. 2021. graf
Article in Spanish | LILACS | ID: biblio-1287245

ABSTRACT

Resumen La enfermedad de Whipple es una enfermedad multisistémica crónica, causada por la bacteria Tropherima whipplei. Se han descripto aproximadamente 1200 casos en la literatura. La incidencia mundial se estima en 9.8 casos por millón de personas. Los datos provenientes de Sudamérica y Europa muestran que afecta a varones de mediana edad. Se cree que los factores inmunológicos del huésped son los que influyen en el curso de la infección y no el genotipo del agente. Dado que las características clínicas no suelen ser específicas y el espectro de manifestaciones en órganos individuales puede ser subestimado, el diagnóstico sigue siendo muy difícil. Presentamos un caso confirmado por histopatología con compromiso multisistémico. Consideramos importante su difusión dados los escasos casos documentados en Sudamérica y la relevancia de tener presente la sospecha diagnóstica para el abordaje terapéutico precoz que mejora el pronóstico de esta rara enfermedad.


Abstract Whipple's disease is a chronic mutisystem disease caused by the bacteria Tropherima whipplei. Approximately 1200 cases have been described in the literature. The worldwide incidence is estimated at 9.8 cases per million people. Data from South America and Europe show that it affects middle-aged males. It is believed that host immunological factors rather than agent genotypic traits influence the course of the infection. Since the clinical characteristics are usually nonspecific and the wide spectrum of manifestations in individual organs may be underestimated, the diagnosis remains challenging. We present a case with multisystem compromise confirmed by histopathology. We consider its publication important given the few cases documented in South America and the relevance of bearing in mind the importance of an early diagnosis for a prompt treatment that improves the prognosis of this rare disease.


Subject(s)
Humans , Male , Middle Aged , Aged , Hypertension, Pulmonary/diagnosis , Hypertension, Pulmonary/etiology , Whipple Disease/complications , Whipple Disease/diagnosis , Whipple Disease/drug therapy , Europe , Tropheryma , Anti-Bacterial Agents/therapeutic use
2.
Medicina (B Aires) ; 81(1): 91-95, 2021.
Article in Spanish | MEDLINE | ID: mdl-33611249

ABSTRACT

Whipple's disease is a chronic mutisystem disease caused by the bacteria Tropherima whipplei. Approximately 1200 cases have been described in the literature. The worldwide incidence is estimated at 9.8 cases per million people. Data from South America and Europe show that it affects middle-aged males. It is believed that host immunological factors rather than agent genotypic traits influence the course of the infection. Since the clinical characteristics are usually nonspecific and the wide spectrum of manifestations in individual organs may be underestimated, the diagnosis remains challenging. We present a case with multisystem compromise confirmed by histopathology. We consider its publication important given the few cases documented in South America and the relevance of bearing in mind the importance of an early diagnosis for a prompt treatment that improves the prognosis of this rare disease.


La enfermedad de Whipple es una enfermedad multisistémica crónica, causada por la bacteria Tropherima whipplei. Se han descripto aproximadamente 1200 casos en la literatura. La incidencia mundial se estima en 9.8 casos por millón de personas. Los datos provenientes de Sudamérica y Europa muestran que afecta a varones de mediana edad. Se cree que los factores inmunológicos del huésped son los que influyen en el curso de la infección y no el genotipo del agente. Dado que las características clínicas no suelen ser específicas y el espectro de manifestaciones en órganos individuales puede ser subestimado, el diagnóstico sigue siendo muy difícil. Presentamos un caso confirmado por histopatología con compromiso multisistémico. Consideramos importante su difusión dados los escasos casos documentados en Sudamérica y la relevancia de tener presente la sospecha diagnóstica para el abordaje terapéutico precoz que mejora el pronóstico de esta rara enfermedad.


Subject(s)
Hypertension, Pulmonary , Whipple Disease , Aged , Anti-Bacterial Agents/therapeutic use , Europe , Humans , Hypertension, Pulmonary/diagnosis , Hypertension, Pulmonary/etiology , Male , Middle Aged , Tropheryma , Whipple Disease/complications , Whipple Disease/diagnosis , Whipple Disease/drug therapy
3.
Pharmaceutics ; 12(9)2020 Sep 22.
Article in English | MEDLINE | ID: mdl-32971783

ABSTRACT

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.

4.
Front. med. (En línea) ; 14(2): 85-87, abr.-jun. 2019. ilus
Article in Spanish | LILACS | ID: biblio-1103190

ABSTRACT

Anteriormente la neoplasia quística mucinosa del hígado (NQM-H) se había clasificado como cistoadenoma biliar o cistoadenocarcinoma biliar. Sin embargo, la Organización Mundial de la Salud en la clasificación del 2010 definió la NQM-H como contrapartida de la NQM del páncreas (NQM-P). En ambos casos se requiere la presencia de estroma ovárico para establecer el diagnóstico. La NQM-H es una rara enfermedad que se produce en una frecuencia mucho menor que la pancreática y sus características biológicas han sido poco esclarecidas. Presentamos un caso de NQM-H en una paciente de 33 años que fue tratada con resección quirúrgica.(AU)


Subject(s)
Neoplasms, Cystic, Mucinous, and Serous , Liver
5.
JAMA Ophthalmol ; 136(7): 747-752, 2018 07 01.
Article in English | MEDLINE | ID: mdl-29799944

ABSTRACT

Importance: Multi-institutional collaborative studies that include large patient populations for the management of retinoblastoma with histopathological risk factors could provide important information for patient management. Objective: To evaluate the implementation of a strategy for the management of nonmetastatic unilateral retinoblastoma in children based on standardized diagnostic and treatment criteria. Design, Setting, and Participants: This single-arm prospective study applied a strategy based on a single-center experience. The setting was a multicenter study in Latin America (Grupo de America Latina de Oncologia Pediatrica [GALOP]). Participants were children with nonmetastatic unilateral retinoblastoma (staged with the International Retinoblastoma Staging System). The study opened on July 1, 2008, and closed on December 31, 2014. Follow-up was updated until June 30, 2017. Interventions: Stage 0 patients (without enucleation) were given conservative therapy without a protocol. Stage I patients (with enucleation and no residual tumor) were divided into a high-risk group (retrolaminar invasion and/or scleral invasion) and a low-risk group (all remaining patients). High-risk children received adjuvant chemotherapy with 4 alternating cycles of regimen 1 (cyclophosphamide [65 mg/kg/d] [plus sodium-2-mercaptoethane sulfonate], idarubicin hydrochloride [10 mg/m2/d], and vincristine sulfate [0.05 mg/kg/d]) and 4 cycles of regimen 2 (carboplatin [500 mg/m2/d, days 1 and 2] and etoposide [100 mg/m2/d, days 1-3]). Low-risk children did not receive adjuvant therapy. Children with buphthalmia received neoadjuvant and adjuvant chemotherapy for a total of 8 cycles. Main Outcomes and Measures: Probability of event-free survival (extraocular relapse and death from any cause were considered events). Results: Among 187 children registered in the study, 175 were evaluable (92 [52.5%] female; median age, 22 months; age range, 3-100 months). Forty-two were stage 0 children, 84 were stage I low-risk children, and 42 were stage I high-risk children; there were 7 children in the buphthalmia group. With a median follow-up of 46 months, the 3-year probability of event-free survival was 0.97 (95% CI, 0.94-0.99), and the probability of overall survival was 0.98 (95% CI, 0.94-1.00). Stage 0 patients had no events, stage I low-risk patients had 1 event (orbital relapse treated with second-line therapy), stage I high-risk patients had 2 events (1 central nervous system relapse and 1 death from sepsis), and the buphthalmia group had 1 event (orbital relapse, followed by central nervous relapse and death). Conclusions and Relevance: Adjuvant therapy may be effective for high-risk unilateral retinoblastoma but is toxic, and neoadjuvant chemotherapy for buphthalmus appears feasible.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Retinal Neoplasms/drug therapy , Retinoblastoma/drug therapy , Carboplatin/administration & dosage , Child , Child, Preschool , Cyclophosphamide/administration & dosage , Disease-Free Survival , Etoposide/administration & dosage , Eye Enucleation , Female , Humans , Hydrophthalmos/complications , Idarubicin/administration & dosage , Infant , Male , Mesna/administration & dosage , Neoplasm Metastasis , Neoplasm Staging , Prospective Studies , Retinal Neoplasms/mortality , Retinal Neoplasms/pathology , Retinoblastoma/mortality , Retinoblastoma/pathology , Survival Rate , Vincristine/administration & dosage
6.
Ther Drug Monit ; 40(4): 401-410, 2018 08.
Article in English | MEDLINE | ID: mdl-29621122

ABSTRACT

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.


Subject(s)
Graft Rejection/epidemiology , Liver Transplantation/statistics & numerical data , Tacrolimus/adverse effects , Argentina/epidemiology , Child, Preschool , Cytochrome P-450 CYP3A/genetics , Female , Genotype , Humans , Immunosuppressive Agents/adverse effects , Immunosuppressive Agents/blood , Kaplan-Meier Estimate , Male , Polymorphism, Genetic/genetics , Retrospective Studies , Risk Factors , Tacrolimus/blood
7.
Rev. argent. microbiol ; 48(2): 110-118, jun. 2016. graf, tab
Article in English | LILACS | ID: biblio-843156

ABSTRACT

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.


Subject(s)
Child , Child, Preschool , Humans , Infant , Postoperative Complications/virology , Viremia/diagnosis , Heart Transplantation , Kidney Transplantation , Liver Transplantation , Herpesvirus 4, Human/isolation & purification , Epstein-Barr Virus Infections/virology , Lymphoproliferative Disorders/virology , Postoperative Complications/diagnosis , Postoperative Complications/etiology , DNA, Viral/blood , Leukocytes, Mononuclear/virology , Cross-Sectional Studies , Retrospective Studies , Follow-Up Studies , Immunocompromised Host , Viral Load , Epstein-Barr Virus Infections/diagnosis , Early Detection of Cancer , Real-Time Polymerase Chain Reaction , Lymphoid Tissue/virology , Lymphoma/diagnosis , Lymphoma/etiology , Lymphoma/virology , Lymphoproliferative Disorders/diagnosis , Lymphoproliferative Disorders/etiology
8.
Rev Argent Microbiol ; 48(2): 110-8, 2016.
Article in English | MEDLINE | ID: mdl-27157146

ABSTRACT

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.


Subject(s)
Epstein-Barr Virus Infections/virology , Heart Transplantation , Herpesvirus 4, Human/isolation & purification , Kidney Transplantation , Liver Transplantation , Lymphoproliferative Disorders/virology , Postoperative Complications/virology , Viremia/diagnosis , Child , Child, Preschool , Cross-Sectional Studies , DNA, Viral/blood , Early Detection of Cancer , Epstein-Barr Virus Infections/diagnosis , Follow-Up Studies , Humans , Immunocompromised Host , Infant , Leukocytes, Mononuclear/virology , Lymphoid Tissue/virology , Lymphoma/diagnosis , Lymphoma/etiology , Lymphoma/virology , Lymphoproliferative Disorders/diagnosis , Lymphoproliferative Disorders/etiology , Postoperative Complications/diagnosis , Postoperative Complications/etiology , Real-Time Polymerase Chain Reaction , Retrospective Studies , Viral Load
9.
Pediatr Blood Cancer ; 62(12): 2120-4, 2015 Dec.
Article in English | MEDLINE | ID: mdl-26154941

ABSTRACT

BACKGROUND: Pediatric neuroectodermal malignancies express N-glycolylated gangliosides including N-glycolyl GM3 (NeuGcGM3) as targets for immunotherapy. PROCEDURE: We evaluated the toxicity and maximum tolerated dose and immunological response of racotumomab, an anti-idiotype vaccine targeting NeuGcGM3 through a Phase I study enrolling children with relapsed or resistant tumors expressing NeuGcGM3. MATERIALS AND METHODS: Drug dose was escalated to three levels (0.15-0.25-0.4 mg) of racotumomab administered intradermally. Each drug level included three patients receiving a total of three doses, every 14 days. A confirmation cohort was added to the highest dose level. Antibody response was assessed upon study entry and at 4-week intervals for at least three immunological determinations for each patient. RESULTS: Fourteen patients were enrolled (10 with neuroblastoma, one with retinoblastoma, one with Wilms' tumor, and two with brainstem glioma). Three patients completed the three drug levels and three were enrolled in the confirmation cohort. One patient died of tumor progression before completing the three applications. Racotumomab was well tolerated. The only side effect observed was grade 1-2 toxicity at the injection site. Racotumomab elicited an IgM and/or IgG antibody response directed against NGcGM3 in nine patients and IgM against racotumomab in 11 of 13 evaluable patients. The maximum tolerated dose was not reached and no dose-limiting toxicity was seen. CONCLUSIONS: Racotumomab vaccination has a favorable toxicity profile up to a dose of 0.4 mg, and most patients elicited an immune response. Its activity as immunotherapy for neuroectodermal malignancies will be tested in further clinical trials.


Subject(s)
Antibodies, Monoclonal/administration & dosage , Brain Stem Neoplasms/drug therapy , Cancer Vaccines/administration & dosage , Drug Resistance, Neoplasm/drug effects , Glioma/drug therapy , Neuroblastoma/diet therapy , Wilms Tumor/drug therapy , Antibodies, Monoclonal, Murine-Derived , Antibodies, Neoplasm/blood , Brain Stem Neoplasms/blood , Child , Child, Preschool , Female , Gangliosides/biosynthesis , Gene Expression Regulation, Neoplastic , Glioma/blood , Humans , Immunoglobulin G/blood , Immunoglobulin M/blood , Infant , Male , Neuroblastoma/blood , Vaccination , Wilms Tumor/blood
10.
JAMA Ophthalmol ; 133(7): 805-12, 2015 Jul.
Article in English | MEDLINE | ID: mdl-25928893

ABSTRACT

IMPORTANCE: Disseminated retinoblastoma is usually fatal. Identification of small amounts (minimal dissemination [MD]) of tumor cells in extraocular sites might be a tool for designing appropriate treatments. OBJECTIVE: To test cone-rod homeobox (CRX) transcription factor as a lineage-specific molecular marker for metastatic retinoblastoma and for evaluation of MD. DESIGN, SETTING, AND PARTICIPANTS: In a prospective cohort design study, we evaluated CRX messenger RNA (mRNA) by retrotranscription followed by real-time polymerase chain reaction as a diagnostic test in samples obtained from bone marrow, peripheral blood, and cerebrospinal fluid (CSF) at diagnosis, after induction chemotherapy, and during follow-up. The study was conducted from June 30, 2008, to June 30, 2014. Seventeen retinoblastoma primary tumors, 2 retinoblastoma cell lines, and 47 samples of bone marrow from other cancers (controls) were studied. Seventeen patients with metastatic retinoblastoma (9 at diagnosis, 8 at relapse; age range: 18-41 months) were included. MAIN OUTCOMES AND MEASURES: Detection of CRX mRNA as a marker for metastatic retinoblastoma and MD in bone marrow and CSF and its correlation with clinical findings. RESULTS: Cone-rod homeobox mRNA was expressed in all tumors (relative expression levels range, 8.1 × 10-5 to 5.6) and cell lines. In control samples, there was no amplification of CRX; only the housekeeping gene (GAPDH) demonstrated amplification. Bone marrow metastatic cells showed expression of CRX mRNA in all 9 children presenting with metastasis at the diagnosis (relative expression levels, 6.0 × 10-5 to 0.67). After induction chemotherapy, no evidence of MD of tumor cells was seen in any of the 8 responding children since only GAPDH showed amplification. In the CSF of children who had a metastatic relapse, CRX mRNA detection was positive in 2 patients in whom no conclusive results were reached by immunocytology for disialoganglioside GD2. Minimal dissemination in the CSF was associated with a clinical relapse in 2 cases. No concomitant MD was evident in the bone marrow in any case. CONCLUSIONS AND RELEVANCE: These data suggest that CRX mRNA is a novel marker for retinoblastoma at extraocular sites. In this study among patients with bone marrow metastasis, there was a quick, complete, and sustained molecular response after induction chemotherapy. In all patients with secondary metastasis, CSF relapse occurred independently from the bone marrow, suggesting a sanctuary site.


Subject(s)
Genetic Predisposition to Disease/epidemiology , Homeodomain Proteins/genetics , Retinal Neoplasms/genetics , Retinoblastoma/genetics , Trans-Activators/genetics , Child, Preschool , Cohort Studies , Female , Follow-Up Studies , Gene Expression Regulation, Neoplastic , Humans , Incidence , Infant , Male , Neoplasm Invasiveness/pathology , Neoplasm Metastasis , Neoplasm Staging , Prospective Studies , RNA, Messenger/genetics , Real-Time Polymerase Chain Reaction/methods , Retinal Neoplasms/epidemiology , Retinal Neoplasms/pathology , Retinoblastoma/epidemiology , Retinoblastoma/secondary , Risk Assessment , Sensitivity and Specificity , Survival Analysis , Transcription Factors/genetics
11.
Pediatr Dev Pathol ; 18(2): 117-21, 2015.
Article in English | MEDLINE | ID: mdl-25535833

ABSTRACT

Ullrich-Turner syndrome (UTS) is a common chromosomal abnormality caused by partial or complete X chromosome monosomy. One half of the patients have a 45,X karyotype, whereas the remaining patients display other X chromosome anomalies. In 6% to 11% of UTS, a normal or partly deleted Y chromosome has been found. A 10% to 30% risk of developing gonadoblastoma was found in the latter patients. The aim of this study was to evaluate the prevalence of Y chromosome-derived material, the occurrence of gonadoblastoma, and the incidence of possible neoplasms in patients with UTS. Of 217 patients studied with UTS and chromosome analysis of peripheral-blood lymphocytes, Y chromosome material was found in 20 patients. Fluorescence in situ hybridization (FISH) testing was performed to characterize the structurally abnormal Y chromosome in 13 cases. Molecular analysis of the SRY gene could only be performed in 20 patients with 45,X karyotype. Two patients had the SRY genomes. Of the 20 patients with Y chromosome-derived material, 17 underwent gonadectomy. The incidence of gonadoblastoma development in our series was 35.5%. Furthermore, 1 patient also showed a pure dysgerminoma, and another showed a mixed dysgerminoma and embryonal carcinoma. We emphasize the importance of complete processing of the gonadectomy specimen, including step sections, molecular studies, and FISH, in addition to the classic cytogenetic searching for Y chromosome sequences, in patients who present with a nonmosaic 45,X karyotype. Finally, we propose to routinely collect a sample for storage in the tumor bank for future studies.


Subject(s)
Chromosomes, Human, X/genetics , Chromosomes, Human, Y/genetics , Gonadoblastoma/genetics , Ovarian Neoplasms/genetics , Turner Syndrome/genetics , Adolescent , Argentina/epidemiology , Child , Child, Preschool , Female , Genetic Predisposition to Disease , Gonadoblastoma/epidemiology , Gonadoblastoma/pathology , Gonadoblastoma/surgery , Humans , In Situ Hybridization, Fluorescence , Incidence , Karyotype , Karyotyping , Mosaicism , Ovarian Neoplasms/epidemiology , Ovarian Neoplasms/pathology , Ovarian Neoplasms/surgery , Phenotype , Sex-Determining Region Y Protein/genetics , Treatment Outcome , Turner Syndrome/epidemiology , Turner Syndrome/pathology
12.
J Pediatr Hematol Oncol ; 36(8): e509-12, 2014 Nov.
Article in English | MEDLINE | ID: mdl-24732059

ABSTRACT

We report a retrospective review of patients with retinoblastoma and anterior segment invasion (ASI) as risk factors for extraocular relapse. Only those with ASI combined with postlaminar optic nerve invasion and/or scleral invasion received adjuvant chemotherapy and those with tumor at the resection margin received orbital radiotherapy. Those with only uveal invasion did not receive adjuvant therapy. Of 479 evaluable patients, 67 patients had pathologically confirmed ASI, including 52 with anterior chamber invasion and 47 with iris or ciliary body invasion. ASI occurred with other pathology risk factors (25 had concomitant posterior uveal invasion, 36 had postlaminar optic nerve invasion, 11 with cut-end invasion, and 25 with scleral invasion). The 5-year disease-free survival (pDFS) was 0.9 (95% CI, 0.8-0.95) for children with ASI with no significant differences among children with other pathology risk factors with and without ASI. ASI was not significantly associated with extraocular relapse in multivariate analysis. There were no significant differences in pDFS for patients with anterior chamber invasion and those with iris-ciliary body invasion (pDFS 0.89 [95% CI, 0.65-0.96] vs. 0.93 [95% CI, 0.61-0.98]). To conclude, ASI was seen with other pathology risk factors and it did not add a significant risk for extraocular relapse.


Subject(s)
Anterior Eye Segment/pathology , Retinal Neoplasms/epidemiology , Retinal Neoplasms/pathology , Retinoblastoma/epidemiology , Retinoblastoma/pathology , Chemotherapy, Adjuvant , Child , Ciliary Body/pathology , Humans , Infant , Iris/pathology , Neoplasm Invasiveness , Optic Nerve/pathology , Recurrence , Retinal Neoplasms/drug therapy , Retinoblastoma/drug therapy , Retrospective Studies , Risk Factors , Sclera/pathology
13.
Mod Pathol ; 27(3): 472-91, 2014 Mar.
Article in English | MEDLINE | ID: mdl-24008558

ABSTRACT

Liver tumors are rare in children, and their diagnoses may be challenging particularly because of the lack of a current consensus classification system. Systematic central histopathological review of these tumors performed as part of the pediatric collaborative therapeutic protocols has allowed the identification of histologic subtypes with distinct clinical associations. As a result, histopathology has been incorporated within the Children's Oncology Group (COG) protocols, and only in the United States, as a risk-stratification parameter and for patient management. Therefore, the COG Liver Tumor Committee sponsored an International Pathology Symposium in March 2011 to discuss the histopathology and classification of pediatric liver tumors, and hepatoblastoma in particular, and work towards an International Pediatric Liver Tumors Consensus Classification that would be required for international collaborative projects. Twenty-two pathologists and experts in pediatric liver tumors, including those serving as central reviewers for the COG, European Société Internationale d'Oncologie Pédiatrique, Gesellschaft für Pädiatrische Onkologie und Hämatologie, and Japanese Study Group for Pediatric Liver Tumors protocols, as well as pediatric oncologists and surgeons specialized in this field, reviewed more than 50 pediatric liver tumor cases and discussed classic and newly reported entities, as well as criteria for their classification. This symposium represented the first collaborative step to develop a classification that may lead to a common treatment-stratification system incorporating tumor histopathology. A standardized, clinically meaningful classification will also be necessary to allow the integration of new biological parameters and to move towards clinical algorithms based on patient characteristics and tumor genetics, which should improve future patient management and outcome.


Subject(s)
Hepatoblastoma/classification , Hepatoblastoma/diagnosis , Liver Neoplasms/classification , Liver Neoplasms/diagnosis , Child , Humans , Los Angeles , Pediatrics
14.
JAMA Ophthalmol ; 131(9): 1127-34, 2013 Sep.
Article in English | MEDLINE | ID: mdl-23787805

ABSTRACT

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.


Subject(s)
Bone Marrow Neoplasms/secondary , Brain Neoplasms/secondary , Optic Nerve Neoplasms/secondary , Retinal Neoplasms/pathology , Retinoblastoma/secondary , Bone Marrow Neoplasms/therapy , Brain Neoplasms/therapy , Child, Preschool , Disease-Free Survival , Eye Enucleation , Follow-Up Studies , Humans , Infant , Neoadjuvant Therapy , Neoplasm Invasiveness , Neoplasm Staging , Optic Disk/pathology , Optic Nerve Neoplasms/therapy , Retinal Neoplasms/therapy , Retinoblastoma/therapy , Retrospective Studies , Risk Factors , Treatment Outcome
15.
Eur J Cancer ; 49(13): 2892-9, 2013 Sep.
Article in English | MEDLINE | ID: mdl-23721779

ABSTRACT

AIM: To evaluate minimally disseminated disease (MDD) in cytologically negative cerebrospinal fluid (CSF) specimens of patients with high-risk retinoblastoma by the detection of the synthase of ganglioside GD2 mRNA by reverse transcriptase-polymerase chain reaction (RT-PCR). METHODS: The CSF was evaluated in 26 patients with high risk for CSF relapse: 14 with postlaminar optic nerve invasion, five of them with tumour at the resection margin, five with massive choroidal invasion, three with overt orbital extension and four patients with systemic metastasis. Serial CSF examinations were repeated at different time intervals according to stage and in the event of suspected relapse. GD2 synthase mRNA was evaluated by RT and nested PCR at each procedure. RESULTS: MDD was present at diagnosis in six cases (23%) and it was significantly associated to massive optic nerve involvement or history of glaucoma (p<0.05). Three of the children with positive MDD had a CSF relapse. Thirteen patients had negative MDD at diagnosis and one had a CSF relapse. In seven children no ARN could be obtained for PCR analysis and two subsequently relapsed. The probability of CSF relapse was 0.50 (95% confidence interval (CI) 0.13-0.88) for children with MDD and 0.08 (95% CI 0.02-0.46) for those with negative RT-PCR examination of the CSF at diagnosis (p=0.03). CONCLUSIONS: MDD in the CSF detected by RT-PCR for GD2-synthase mRNA occurred in 31.7% of evaluable high-risk children with retinoblastoma with no initial central nervous system (CNS) involvement. It was significantly associated to optic nerve involvement and glaucoma and increased risk of CSF relapse.


Subject(s)
Biomarkers, Tumor/cerebrospinal fluid , Biomarkers, Tumor/genetics , N-Acetylgalactosaminyltransferases/genetics , RNA, Messenger/cerebrospinal fluid , Retinal Neoplasms/cerebrospinal fluid , Retinal Neoplasms/genetics , Retinoblastoma/cerebrospinal fluid , Retinoblastoma/genetics , Reverse Transcriptase Polymerase Chain Reaction , Age Factors , Chi-Square Distribution , Choroid/pathology , Disease-Free Survival , Humans , Kaplan-Meier Estimate , Neoplasm Invasiveness , Neoplasm Recurrence, Local , Optic Nerve/pathology , Predictive Value of Tests , Retinal Neoplasms/mortality , Retinal Neoplasms/pathology , Retinal Neoplasms/therapy , Retinoblastoma/mortality , Retinoblastoma/secondary , Retinoblastoma/therapy , Risk Factors , Time Factors , Treatment Outcome
16.
Arch Ophthalmol ; 130(6): 724-9, 2012 Jun.
Article in English | MEDLINE | ID: mdl-22801832

ABSTRACT

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.


Subject(s)
Choroid Neoplasms/pathology , Retinal Neoplasms/pathology , Retinoblastoma/pathology , Adolescent , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Child , Child, Preschool , Choroid Neoplasms/mortality , Choroid Neoplasms/therapy , Disease-Free Survival , Eye Enucleation , Female , Follow-Up Studies , Humans , Infant , Magnetic Resonance Imaging , Male , Neoplasm Grading , Neoplasm Invasiveness , Retinal Neoplasms/mortality , Retinal Neoplasms/therapy , Retinoblastoma/mortality , Retinoblastoma/therapy , Retrospective Studies , Risk Factors , Survival Rate , Tomography, X-Ray Computed
17.
Pediatr Dev Pathol ; 15(1): 65-70, 2012.
Article in English | MEDLINE | ID: mdl-21711207

ABSTRACT

A coexistence of different renal tumors has rarely been reported. The most commonly described association is of Wilms tumor and renal cell carcinoma. Metanephric adenofibroma has also been associated with Wilms tumor or papillary renal cell carcinoma. Another reported association is metanephric adenoma and papillary renal cell carcinoma with sarcomatoid dedifferentiation. Herein we describe a complex renal tumor containing areas of metanephric adenofibroma, Wilms tumor, and undifferentiated renal cell carcinoma in a previously healthy 18-year-old boy. The tumor showed histologic and immunohistochemical features of these 3 different tumors, offering additional support to the view that these 3 tumors are related.


Subject(s)
Adenofibroma/diagnosis , Carcinoma, Renal Cell/diagnosis , Kidney Neoplasms/diagnosis , Neoplasms, Multiple Primary/diagnosis , Wilms Tumor/diagnosis , Adenofibroma/metabolism , Adenofibroma/therapy , Adolescent , Biomarkers, Tumor/metabolism , Carcinoma, Renal Cell/metabolism , Carcinoma, Renal Cell/secondary , Carcinoma, Renal Cell/therapy , Combined Modality Therapy , Fatal Outcome , Humans , Kidney Neoplasms/metabolism , Kidney Neoplasms/therapy , Male , Neoplasm Recurrence, Local , Neoplasms, Multiple Primary/metabolism , Neoplasms, Multiple Primary/secondary , Neoplasms, Multiple Primary/therapy , Nephrectomy , Wilms Tumor/metabolism , Wilms Tumor/secondary , Wilms Tumor/therapy
19.
Arch Argent Pediatr ; 109(1): 68-73, 2011 Feb.
Article in Spanish | MEDLINE | ID: mdl-21283948

ABSTRACT

Eosinophilic gastroenteropathy (EoG) is an uncommon disease characterized by eosinophilic infiltration of the gastrointestinal (GI) mucosa. A chart review was performed searching for patients diagnosed between 2000 and 2010. EoG was diagnosed based on mucosal infiltration of 20 or more eosinophils/HPF in upper GI tract and more than 60 eosinophils/HPF in lower GI tract. Ten patients [median age: 10 mo. (r 2 mo.- 10 yr.)], 9 males, were diagnosed. Four presented with severe protracted diarrhea and weight loss, 2/10 abdominal distention and weight loss and 4/10 protein-losing enteropathy. Exclusive elemental or hypoallergenic diets were administered depending on the age of presentation with remission achieved in 4/10. Six required methylprednisolone to induce remission, 5 are still on budesonide. Due to the emergence of many cases of EoG in the last decade, we should increase our level of suspicion. Multicenter studies could contribute to define the best therapeutic approach for these patients.


Subject(s)
Enteritis , Eosinophilia , Gastritis , Child , Child, Preschool , Enteritis/diagnosis , Enteritis/therapy , Eosinophilia/diagnosis , Eosinophilia/therapy , Female , Gastritis/diagnosis , Gastritis/therapy , Humans , Infant , Male , Retrospective Studies
20.
Clin Gastroenterol Hepatol ; 9(2): 145-9, 2011 Feb.
Article in English | MEDLINE | ID: mdl-21029789

ABSTRACT

BACKGROUND & AIMS: Patients with autoimmune hepatitis (AIH) frequently have liver failure (LF) at the time of diagnosis; their response to immunosuppressive therapy has not been thoroughly analyzed. We evaluated the outcomes of children with AIH and LF who received immunosuppressive therapy and analyzed predictors of liver function recovery. METHODS: We collected data from 237 children that had AIH between September 1996 and December 2008; 50 had LF (defined as prothrombin time <50%) and had not received prior treatment. Patients were treated with either 2 mg/kg/day prednisone at doses up to 60 mg/day (n = 13) or 1 mg/kg/day prednisone at doses up to 40 mg/day plus cyclosporine at blood levels of 200 ± 50 ng/mL (n = 37). RESULTS: Of the 50 patients studied, 45 (90%) achieved prothrombin time >50% in a median time of 24 days (range of 4-257 days); 93% of these patients achieved this within the first 90 days of treatment. Two of the 45 patients who responded to immunosuppression required liver transplantation because of complications related to portal hypertension, and 3 died because of infection. Three of the 5 nonresponders received liver transplants - 1 remained on the waiting list, and the other died because of central nervous system bleeding. Infection was the only independently associated significant factor that delayed recovery from LF (odds ratio = 7.7, 95% confidence interval, 1.5-40). Each therapeutic approach had similar efficacy. CONCLUSIONS: Most pediatric patients with AIH recover after LF with immunosuppressive therapy; liver transplantation could be avoided or delayed. Infection was the most frequent cause of morbidity and mortality in these patients.


Subject(s)
Cyclosporine/therapeutic use , Glucocorticoids/therapeutic use , Hepatitis, Autoimmune/drug therapy , Immunosuppressive Agents/therapeutic use , Liver Failure/therapy , Prednisone/therapeutic use , Adolescent , Bilirubin/blood , Child , Child, Preschool , Drug Therapy, Combination , Female , Hepatitis, Autoimmune/complications , Humans , Infections/complications , Infections/mortality , Liver Failure/etiology , Liver Transplantation , Male , Prothrombin Time , Retrospective Studies , Transaminases/blood , gamma-Globulins/analysis , gamma-Glutamyltransferase/blood
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