Gastrointestinal tract and liver graft-versus-host disease in pediatric patients with hematopoietic progenitor cell transplantation at a tertiary care center in Mexico. / Enfermedad injerto contra huésped gastrointestinal y hepático en pacientes pediátricos con trasplante de células progenitoras hematopoyéticas en el Hospital Infantil de México Federico Gómez.

INTRODUCTION AND AIMS: Graft-versus-host disease (GVHD) is a common multisystemic complication of allogeneic hematopoietic cell transplantation. The most frequent presentations of graft-versus-host disease involve the skin, the gastrointestinal tract, and the liver. The aim of the present study was to know the frequency of gastrointestinal tract and liver GVHD and the characteristics of disease presentation in pediatric patients that underwent hematopoietic stem cell transplantation (HSCT) at a tertiary care hospital center in Mexico City. MATERIAL AND METHODS: A retrospective study was carried out, utilizing the case records of patients that underwent HSCT in 2015, to determine the frequency of GVHD in pediatric patients at a Mexican tertiary care hospital center. RESULTS: In 2015, 16 HSCT were performed, 11 of which were carried out in males (68%). Only 3 patients developed graft-versus-host disease (18.7%). One patient presented with skin and liver GVHD and 2 patients presented with gastrointestinal tract and liver GVHD, which was the most frequent type. CONCLUSIONS: HSCT is still an uncommon procedure in Mexico and there is a lower frequency of gastrointestinal tract and liver GVHD than that reported in other studies. Most certainly, there will be an increase in this type of patient and risk factors in the Mexican population must still be determined to help predict the onset of GVHD.

Illumina next generation sequencing data and expression microarrays data from retinoblastoma and medulloblastoma tissues.

Retinoblastoma (Rb) is a pediatric intraocular malignancy and probably the most robust clinical model on which genetic predisposition to develop cancer has been demonstrated. Since deletions in chromosome 13 have been described in this tumor, we performed next generation sequencing to test whether recurrent losses could be detected in low coverage data. We used Illumina platform for 13 tumor tissue samples: two pools of 4 retinoblastoma cases each and one pool of 5 medulloblastoma cases (raw data can be found at http://www.ebi.ac.uk/ena/data/view/PRJEB6630). We first created an in silico reference profile generated from a human sequenced genome (GRCh37p5). From this data we calculated an integrity score to get an overview of gains and losses in all chromosomes; we next analyzed each chromosome in windows of 40 kb length, calculating for each window the log2 ratio between reads from tumor pool and in silico reference. Finally we generated panoramic maps with all the windows whether lost or gained along each chromosome associated to its cytogenetic bands to facilitate interpretation. Expression microarrays was done for the same samples and a list of over and under expressed genes is presented here. For this detection a significance analysis was done and a log2 fold change was chosen as significant (raw data can be found at http://www.ncbi.nlm.nih.gov/geo/accession number GSE11488). The complete research article can be found at Cancer Genetics journal (Garcia-Chequer et al., in press) [1]. In summary here we provide an overview with visual graphics of gains and losses chromosome by chromosome in retinoblastoma and medulloblastoma, also the integrity score analysis and a list of genes with relevant expression associated. This material can be useful to researchers that may want to explore gains and losses in other malignant tumors with this approach or compare their data with retinoblastoma.

Overview of recurrent chromosomal losses in retinoblastoma detected by low coverage next generation sequencing.

Genes are frequently lost or gained in malignant tumors and the analysis of these changes can be informative about the underlying tumor biology. Retinoblastoma is a pediatric intraocular malignancy, and since deletions in chromosome 13 have been described in this tumor, we performed genome wide sequencing with the Illumina platform to test whether recurrent losses could be detected in low coverage data from DNA pools of Rb cases. An in silico reference profile for each pool was created from the human genome sequence GRCh37p5; a chromosome integrity score and a graphics 40 Kb window analysis approach, allowed us to identify with high resolution previously reported non random recurrent losses in all chromosomes of these tumors. We also found a pattern of gains and losses associated to clear and dark cytogenetic bands respectively. We further analyze a pool of medulloblastoma and found a more stable genomic profile and previously reported losses in this tumor. This approach facilitates identification of recurrent deletions from many patients that may be biological relevant for tumor development.

Serum soluble interleukin 2 receptor (sIL-2R) as a marker of acute rejection in renal transplant children.

The aim of the study was to evaluate whether or not serum levels of soluble interleukin 2 receptor (sIL-2R) predict acute rejection in pediatric recipients. We studied 51 pediatric renal transplant recipients divided into three groups: Group 1) Biopsy-proven cellular acute rejection (n = 19), Group 2) Graft dysfunction with histological diagnosis other than acute rejection (n = 8) and Group 3) Patients with stable graft function, no biopsy (n = 24). Serum samples for sIL-2R measurement by sandwich ELISA were obtained at the time of renal transplant and at the time of renal biopsy due to graft dysfunction (Groups 1 and 2) or at six months post-transplant in the case of Group 3. The mean ± s.e. serum values of sIL-2R were higher in patients during acute rejection (6539 ± 1802 pg/mL) compared to patients with other causes of graft dysfunction (2217 ± 256 pg/mL) or stable graft function at six months (2183 ± 283 pg/mL) (Kruskal-Wallis p = 0.004). When the sIL2-R levels at the time of transplant were compared to those at the time of biopsy (Groups 1 and 2) or at six months post-transplant in Group 3, there was no significant difference between baseline and biopsy in the acute rejection group (paired t-test = 0.07), whereas there was a significant reduction in Groups 2 and 3.

Preirradiation ifosfamide, carboplatin, and etoposide for the treatment of anaplastic astrocytomas and glioblastoma multiforme: a phase II study.

BACKGROUND: Central nervous system (CNS) tumors are the second most common pediatric tumors. Astrocytomas represent 35% of all CNS tumors in children. Traditional treatment of anaplastic astrocytoma (AA) and glioblastoma multiforme (GM) consisting of surgery-radiotherapy-chemotherapy with nitrosoureas has resulted in a survival rate of 26% at 1 year. Neoadjuvant chemotherapy has proven good results in the treatment of other solid tumors. Chemotherapy with ifosfamide, carboplatin, and etoposide (ICE) permits synergism among the different drugs and sensitizes the tumor to radiotherapy. Our objective was to evaluate the efficacy, security, and survival rate of postoperative chemotherapy with ICE in pediatric patients with AA or GM. METHODS: Phase II study. We evaluated 11 children with AA or GM who had received no prior treatment. A magnetic resonance image (MRI) study of the tumor was made after surgery to evaluate residual tumor and routine laboratory analysis. Chemotherapy with carboplatin, ifosfamide and etoposide was given every 3 weeks for four courses. MRI studies were repeated after the second and last courses and laboratory analyses were carried out before each course to evaluate toxicity. Each patient then received hyperfractionated radiotherapy and a final MRI was done at the end of the treatment. RESULTS: Sixty percent of the patients had partial response, 30% complete response after two courses, and 60% of CR after four courses. Supratentorial and infratentorial tumors had a good response to chemotherapy. Brainstem tumors had an initial response after two courses and then increased in size. AA was the tumor with the greatest reduction of residual tumor after treatment. Overall and free survival at 53 months was 70%. To date, three patients have died secondary to tumoral progression. There have been no relapses in the seven patients with a CR. CONCLUSIONS: Postoperative chemotherapy with ICE reduces the tumor size and increases the survival rate of pediatric patients with malignant astrocytomas with minimal toxicity. Brainstem responded poorly to treatment.

Cytomegalovirus infection in children: frequency, anatomopathologic characteristics and underlying risk factors in 1618 autopsies.

The aim of this study was to determine the frequency of cytomegalovirus (CMV) infection in children with postmortem study. The records of 1618 autopsies performed during 1980-1989 at the Hospital Infantil de México Federico Gómez were reviewed. Characteristic cytomegalovirus inclusion bodies were identified, in one or several organs, in 47 cases (2.9% of the autopsies). None of these cases was cultured for viruses prior to or at the time of autopsy. Of the 47 cases, 24 (51%) with CMV were younger than 3 months and 38 cases (80%) younger than 12 months of age. In eight cases, the infection was judged as generalized and considered the cause of death. Two of these patients were premature and the infection was most probably intrauterine. The risk factor most frequently identified was secondary immunosuppression. The lung was the most common affected organ, followed by kidney, adrenals, pancreas, liver, brain and salivary glands. In seven cases the inclusion bodies were seen in the brain and in three others periventricular calcifications without inclusion bodies were observed. Although not a rarity in Mexico, CMV infection is not often suspected. Additional studies are needed in order to determine the prevalence of CMV infection in Mexico.

[Disseminated histoplasmosis in children]. / Histoplasmosis diseminada en niños.

Disseminated histoplasmosis is a rare and severe form of the infection due to the fungus Histoplasma capsulatum. This form of disease is seen mainly in patients with some sort of immune deficiency either primary or secondary, in children under two years and in elderly people. An autopsy review at the Hospital Infantil de México Federico Gómez disclosed eight cases of lethal disseminated histoplasmosis in an eight year period. All patients were malnourished, one of them also had a primary immunodeficiency an another had acquired immune deficiency syndrome. The age range was from two months to seven years; five patients were males. The organs more frequently affected were lungs, liver and spleen. In seven patients the diagnosis was established at postmortem study. The patients came from Morelos, Veracruz, Guerrero and Chiapas, regions considered endemic for histoplasmosis. A careful analysis of the clinical symptoms together with a detailed information of the living environment of patients, will lead to an accurate diagnosis and management of children with this disease.

[IgA nephropathy (Berger's disease) in children]. / Nefropatía IgA (enfermedad de Berger) en niños.

IgA nephropathy, also called Berger's disease, is characterized by recurrent gross hematuria or persistent microscopic hematuria, together with mesangial glomerular deposits of IgA found in the renal biopsy. Seven children with IgA nephropathy were studied. Most of them presented initially with recurrent macroscopic hematuria and low or moderate-grade proteinuria, without hypertension or renal function impairment. Only one patient presented with a rapidly progressive glomerulonephritis. Four patients did not receive any treatment; one of them is in remission, one has improved and two remain with moderate proteinuria and hematuria. One patient with significant proteinuria improved after prednisone and azathioprine treatment. The patient with rapidly progressive glomerulonephritis improved his renal function after oral prednisone and intravenous boluses of methylprednisolone and cyclophosphamide.

[Central nervous system pathology in children with AIDS]. / Patología del sistema nervioso central en niños con síndrome de inmunodeficiencia adquirida.

The neuropathological manifestations of AIDS in children vary widely and includes, among others: cerebral atrophy, basal ganglia calcification, corticospinal tract demyelinization, and HIV encephalomyelitis with multinucleated cells. The purpose of this work is to inform the postmortem CNS findings in 14 pediatric AIDS patients which were studied from January 1986 to February 1992, at the Hospital Infantil de México Federico Gómez. Basal ganglia vascular calcification, HIV multinucleated cells, and corticospinal tract demyelinization, were significantly less frequent (P < 0.01) in our patients than those informed in the literature. Opportunistic CNS infections found in our patients were produced by microorganisms commonly described in adults. We think that these differences may be explained because the majority of our patients acquired the infection trough blood transfusion at an age in which the CNS is fully developed. The pattern of HIV transmission in our country has been changing recently with an increase in the number of perinatal cases. We also think that in the near future we will observe a change in the neuropathological findings of our pediatric AIDS population.

[Nephrotic syndrome associated with AIDS in children]. / Síndrome nefrótico asociado al síndrome de inmunodeficiencia adquirida en niños.

Several renal and renal-related disturbances have been described in patients with AIDS (acquired immune deficiency syndrome), in adults and children as well. These are mainly electrolyte and acid-base imbalance, acute renal failure and nephrotic syndrome. The latter is usually steroid non-responder. The renal histopathological lesions described more commonly are minimal change, mesangial hyperplasia and focal segmental glomerulosclerosis. Herein, we describe a 5 year-old with AIDS, that developed nephrotic syndrome, characterized by edema, ascites, hypoalbuminemia and massive proteinuria. A percutaneous renal biopsy showed mesangial proliferation. She did not respond to a 6 week treatment with prednisone. She died with sepsis after several viral and bacterial infections.

[Coronary arteriopathy associated with cardiomyopathy in an adolescent with AIDS]. / Arteriopatía coronaria asociada a cardiomiopatía en un adolescente con síndrome de inmunodeficiencia adquirida.

The purpose of this paper is to inform the case of a 15 years old male patient who died as a consequence of acquired immunodeficiency syndrome (AIDS) complications. The postmortem examination showed a coronary lesion which, to the best of our knowledge, has not been previously described. This vasculopathy was restricted to the coronary arteries; myocardial changes similar to those described in AIDS-associated dilated cardiomyopathy were also present. The coronariopathy was indistinguishable from that described in the blood vessels of the brain in patients with AIDS-related cerebral arteriopathy. We also reviewed the autopsy material from another 14 children who died of AIDS, an in none of them exhibited similar changes in the coronary arteries. In addition we present the clinical findings and some theoretical considerations regarding the pathogenesis of the lesions.

[Congenital cystic adenomatoid malformation of the lung. A report of 12 cases]. / Malformación adenomatoidea quística pulmonar congénita. Presentación de 12 casos.

The congenital cystic adenomatoid malformation of the lung is uncommon. In the Hospital Infantil de México Federico Gómez, 12 cases have been seen over a period of 31 years, which points out how rare this malformation is. There was a male predominance, and 75% of the patients had symptoms by 8 months of age. The main complaints were progressive respiratory failure in the newborn period and recurrent lung infection in older children. Treatment was surgical in all cases. There was only one fatality due to cardiac failure.

Nodular renal blastema and metanephric hamartomas in children with urinary tract malformations: a morphologic spectrum of abnormal metanephric differentiation.

In a retrospective review, we identified a variety of abnormal immature and differentiated metanephric tissues including nodular renal blastema and metanephric hamartomas in 12 children with urinary tract malformations with or without renal dysplasia. Four infants also had trisomy. Nodular renal blastema was characterized by small subcapsular clusters of primitive metanephric cells, in some cases with evidence of tubular, papillary, or trabecular differentiation. Metanephric hamartomas included papillary adenomas and tubular hamartomas. Undifferentiated renal blastema was multifocal, but more differentiated blastema usually occurred as isolated nodules. When accompanied by renal dysplasia, blastema tended to show differentiation. One child had a spectrum of lesions with both blastema and more differentiated metanephric hamartomas.