La Unidad Clínica de Gastroenterología y Hepatología Pediátrica del Hospital Universitario y Politécnico La Fe / The Pediatric Gastroenterology and Hepatology Clinical Unit of the University and Polytechnic Hospital La Fe

La unidad de Gastroenterología y hepatología Pediátrica del Hospital La Fe tiene como misión la atención médica de la patología digestiva de pacientes pediátricos de la Comunidad Valenciana, incluyendo la coordinación de los pacientes afectos de fibrosis quística, un programa de trasplante hepático pediátrico así como una cartera de pruebas funcionales para pacientes propios y externos. Igualmente lleva a cabo una labor de investigación que abarca diferentes aspectos de la enfermedad celíaca, especialmente en el área de diagnóstico. En los últimos años hemos iniciado, junto con la Unidad Hepatología Experimental del Instituto de Investigación Sanitaria La Fe, una línea de investigación en trasplante celular hepático. Numerosas publicaciones en revistas de alto impacto acreditan esta actividad. La labor docente se manifiesta no solo en la formación de residentes del propio centro, sino también en la rotación temporal por nuestro servicio de facultativos externos, y en la organización de cursos y congresos tanto a nivel nacional como internacional (AU)

The Paediatric Gastroenterology and Hepatology Unit of Hospital La Fe aims at taking care of all children with relevant gastrointestinal or liver diseases, either acute or chronic, from the Autonomic community of Valencia; besides we coordinate the assistance of patients with cystic fibrosis, and are responsible for the pediatric liver transplantation program. Our laboratory performs functional tests for in and out patients, such as sweat test, impedanciometry, videocapsule, small intestinal biopsy, absorption test and liver elastography. We have a longstanding tradition of investigation in the field of celiac disease, specially in diagnosis and epidemiology as shown by numerous publications in high impact index papers. More recently we have started a new program on liver cell transplantation together with the Experimental Hepatology Unit (AU)

Autoimmunity as a prognostic factor in sporadic adult onset cerebellar ataxia.

Cerebellar adult onset ataxia is a heterogeneous condition. The aim of this study was to ascertain if there is a heightened autoimmune background in patients with sporadic cerebellar ataxia of unknown origin, and if autoimmunity correlates with a more rapid evolution of the ataxia. We selected patients with sporadic progressive adult onset cerebellar ataxia with a follow-up of >5 years. As controls we included 43 patients with genetically demonstrated hereditary ataxia. All patients were tested for a panel of neuronal (onconeuronal, glutamate-decarboxylase [GAD], IgG/IgA transglutaminase 6 antibodies) and systemic non-neuronal antibodies (including IgG/IgA gliadin and transglutaminase 2, thyroperoxidase, thyroglobulin, antinuclear, striational, smooth muscle, mitochondrial, liver kidney microsomal, and parietal gastric cells antibodies). Correlation between the antibodies and disease progression was studied with Cox regression models and Kaplan-Meier plots. Forty-four patients were included. All patients were negative for onconeuronal or GAD antibodies. There were no significant differences between patients and controls in the prevalence of transglutaminase 6, 2, gliadin, or thyroid antibodies. However, when we studied the panel of systemic non-neuronal autoantibodies as a group, antibodies were more frequent in patients with sporadic ataxia (p = 0.018). The presence of one or more systemic non-neuronal antibodies correlated with a faster evolution to stage 2 (loss of independent gait) (p = 0.03) and shorter survival (p = 0.03) in patients with sporadic ataxia. We conclude that there is probably a heightened autoimmune background in some patients with sporadic cerebellar ataxia of unknown origin. The presence of systemic non-neuronal autoantibodies is a prognostic marker.

Allelic distribution and the effect of haplotype combination for HLA type II loci in the celiac disease population of the Valencian community (Spain).

The association between human leukocyte antigen (HLA) class II antigens and celiac disease (CD) was analyzed in a Spanish population. No association with DRB1*04 and DQB1*0302 was noted. The main associated haplotype (70.8%) was DRB1*03-DQB1*0201-DQA1*0501(DR3-DQ2), followed by DRB1*07-DQB1*0202-DQA1*0201 (DR7-DQ2) haplotype, which is associated with DRB1*11-DQB1*0301-DQA1*0505 (DR11-DQ7). The combinations of DR3-DQ2 with DR7-DQ2, and DR7-DQ2 with DR11-DQ7, present a twofold risk compared with each haplotype in homozygosis. An independence test in DR3-DQ2 haplotype found that association with CD was attributable to the whole haplotype, but for DR7-DQ2 was secondary to DQB1/DQA1. There is no need of a double gene dosage to increase the risk. CD-associated alleles typing demonstrates a very high negative predictive value to exclude CD in risk groups.

Specific duodenal and faecal bacterial groups associated with paediatric coeliac disease.

AIMS: To identify specific gut bacteria associated with coeliac disease (CD) at diagnosis and after treatment with a gluten-free diet (GFD) in a paediatric population. METHODS: 30 and 18 faecal samples from untreated and treated CD patients and 25 and 8 biopsy samples from untreated and treated CD patients, respectively, were analysed. In addition, 30 faecal and 8 biopsy samples from control children were evaluated for comparative purposes. Gut bacterial groups were quantified by real-time PCR. RESULTS: Bacteroides and Clostridium leptum groups were more abundant in faeces and biopsies of CD patients than in controls regardless of the stage of the disease. E coli and Staphylococcus counts were also higher in faeces and biopsies of non-treated CD patients than in those of controls, but their levels were normalised after treatment with a GFD. Bifidobacterium levels were lower in faeces of both groups of CD patients and in biopsies of untreated CD patients compared to controls. Similar bacterial groups were related to CD in biopsies and faeces, indicating that faecal microbiota partly reflects that of the small intestine in CD patients, and could constitute a convenient biological index of this disorder. CONCLUSIONS: Duodenal and faecal microbiota is unbalanced in children with untreated CD and only partially restored after long-term treatment with a GFD, constituting a novel factor linked to this disorder.

Modifying effect of HLA haplotypes located trans to DQB1*02-DRB1*03 in celiac patients of Southern Europe.

The DQ2 heterodimer, encoded by the human leukocyte antigen (HLA)-DQA1*05-DQB1*02 alleles, is the major genetic susceptibility factor for celiac disease (CD). However, the risk associated to HLA alleles varies among populations. While DRB1*03 is almost the only CD susceptibility allele in Northern Europe with a homozygote frequency of around 30%, CD in south European countries is also associated with the DRB1*07, and DRB1*03 homozygotes patients are rare. Some authors have suggested that DQB1*02-DRB1*03/DQB1*02-DRB1*03 and DQB1*02-DRB1*03/DQB1*02-DRB1*07 may confer different risk susceptibility to CD. This hypothesis, however, has not been demonstrated in a recent family-based study carried out in Finland, suggesting that the proposed differences in risk may be secondary to stratification burdens of case-control studies. To assess this issue, we have investigated the effect of different haplotypes carried trans to DQB1*02-DRB1*03 as additional factors for CD in Spain, using two statistical approaches, a case-control study and a family-based study. We found that DQB1*02-DRB1*03/DQB1*02-DRB1*03 and DQB1*02-DRB1*03/DQB1*02-DRB1*07 were the only combinations that showed a strong and independent association to CD. We did not observe any difference in susceptibility risk conferred by DQB1*02-DRB1*03 and DQB1*02-DRB1*07 when carried trans to DQB1*02-DRB1*03, suggesting that variation in HLA haplotype frequencies among populations may not represent real differences in risk to CD development. We also confirmed a gene dosage effect of the DQB1*02-DRB1*03 haplotype estimating that DQB1*02 homozygotes are at fivefold increased risk for CD compared with DQB1*02 heterozygotes. This risk is conferred by the second copy of the DQB1*02 allele and it seems to be independent of the DQA1.

Genetic analyses of celiac disease in a Spanish population confirm association with CELIAC3 but not with CELIAC4.

Genetic predisposition to celiac disease (CD) is determined primarily by the human leukocyte antigen (HLA) genes (CELIAC1 region; 6p21), although many loci are involved in disease susceptibility. First, we have analysed a large series of CD patients from the Spanish Mediterranean region who had previously been characterised for the HLA complex. We have investigated how relevant regions contribute to CD susceptibility: CELIAC3 (CD28/CTLA4/ICOS region on 2q33) and CELIAC4 (19p13) as well as the tumour necrosis factor alpha (TNF-alpha) and the linfotoxin loci by case-control and association analyses. We highlight the association with the +49*A allele of cytotoxic T-lymphocyte-associated antigen 4 locus (P = 0.01), and the -308*A of TNF-alpha locus (P = 0.0008) in DQ2 individuals, although an independent role for TNF-alpha as risk factor has not been proven. Moreover, we do not confirm the association with the CELIAC4 region polymorphisms described in other populations.

Terapia de rehidratación oral en la diarrea aguda / Oral rehydration therapyin acute diarrhea

La diarrea aguda es una de las mayores causas de morbimortalidad tanto en los países subdesarrollados como en los desarrollados. En el tratamiento de este cuadro lo más importante es evitar o corregir la deshidratación con una adecuada solución de rehidratación oral. El conocimiento de la terapia de rehidratación oral es básico para que el pediatra realice un buen tratamiento de la diarrea aguda (AU)

[Prevalence of prostatic intraepithelial neoplasia in Spain]. / Prevalencia de la neoplasia intraepitelial prostática en España.

OBJECTIVE: To study the prevalence of high grade prostatic intraepithelial neoplasia in a Spanish population and to compare it with the prevalence in Caucasians of other countries and Afro-Americans. METHODS: 162 prostates obtained at autopsy from Spanish men aged 20-80 years, were fixed in 10% formalin and slices perpendicular to the posterior margin were made every 3-4 mm along its entire length. All blocks were embedded in paraffin and examined microscopically. Mapping of focality and site of the high grade prostatic intraepithelial neoplasia was done for each case. The Wayne University autopsy study was used for comparison of the prevalence in other countries and races. RESULTS: 146 prostates from men with a mean age of 48.5 years were considered valid for histological analysis. There were 42 high grade prostatic intraepithelial neoplasia; 20 were focal and 22 multifocal. By age group, the prevalence of high grade prostatic intraepithelial neoplasia were 7.1%, 14.7%, 28.5%, 33.3%, 45.4% and 51.8% for the 3rd, 4th, 5th, 6th, 7th, and 8th decades. CONCLUSIONS: High grade prostatic intraepithelial neoplasia begins to manifest in the Spanish population after the 3rd decade. It is usually focal and peripheral, and significantly increases with age and becomes multifocal. Its prevalence in the Spanish population is moderately lower than in American Caucasians and significantly lower than in Afro-Americans.

Cytospins--an alternative method for fine-needle aspiration cytology of the breast: a study of 148 cases.

The aim of this study was to evaluate the cytospin technique as an alternative method to prepare fine-needle aspiration (FNA) specimens of the breast. To do so, the cytology of 148 breast FNAs that had been prepared by the cytospin technique and that had histologic correlation, was reviewed. All the cases that were diagnosed as malignant by cytology were proved malignant after surgical excision, and there were no false-positive results. All but two cases diagnosed as benign by cytology proved to be benign on excision. The two false-negative cases were missed due to sampling error. The cytological features seen on cytospins were similar to those seen on conventional direct smears. The major advantage of this method is that no aspirate is unsatisfactory due to unskilled direct smear technique. This, along with its good correlation with histology, proves that the cytospin method is an effective alternative to conventional direct smears for breast FNA.

Malignant mixed müllerian tumor of the ovary. Report of a case with cytodiagnosis by fine needle aspiration.

An elderly woman with a history of a total hysterectomy underwent fine needle biopsy of an ovarian lesion during laparotomy. The cytologic findings demonstrated adenocarcinomatous and heterologous sarcomatous cells and were reported as a malignant mixed müllerian tumor. A histologic examination confirmed this diagnosis.

Cytodiagnosis of clear cell hepatocellular carcinoma. A case report.

The cytologic features of clear cell hepatocellular carcinoma are described. This tumor may cause a diagnostic dilemma since it resembles other clear cell tumors originating in the adrenals, kidneys and ovaries. However, clear cell hepatocellular carcinoma possesses some characteristic features that permit a cytologic diagnosis to be made by fine needle aspiration, thus contributing to proper management.

The application of fine needle aspiration cytology in the diagnosis of multiple primary malignant tumors.

Four cases with multiple primary malignant tumors are presented. In all cases, fine needle aspiration (FNA) cytologic findings indicated the presence of more than one primary malignancy. In one case, the cytologic examination simultaneously diagnosed two separate primaries. Since FNA cytology can often be used to identify the tumor type, it can be utilized in the identification of many multiple primary malignancies, as these cases show.

Cytologic diagnosis of bronchioloalveolar carcinoma by fine-needle aspiration biopsy.

From 1970 to June 1984, 275 patients with bronchioloalveolar carcinoma were admitted to the Toronto General Hospital. Of these, 181 (190 aspiration biopsies, including nine repeat samples) had this diagnosis made following the use of transthoracic fine-needle aspiration biopsy. Based on the cytomorphologic features observed in the aspiration preparations, the tumor was subclassified into three types: nonsecretory, secretory, and poorly differentiated. The cytologic features of these three types of bronchioloalveolar carcinoma are presented and illustrated. Cytomorphologically, the three types of this tumor are distinctly different and their features are sufficiently distinctive from those of bronchogenic adenocarcinoma and metastatic adenocarcinomas to be of diagnostic value. Transthoracic fine-needle aspiration biopsy appears to be a definitive minimally invasive means of establishing the diagnosis of bronchioloalveolar carcinoma preoperatively and especially to be of value for those small peripheral cancers which are relatively inaccessible to direct method of study and are potentially surgically curable.

Cytologic diagnosis of intravenous talc granulomatosis by fine needle aspiration biopsy. A case report.

A fine needle aspiration specimen from the right lung of a 44-year-old former drug addict was submitted for cytologic evaluation. The specimen consisted of numerous mononucleate and multinucleate macrophages containing aggregates of silicate crystals, as seen by light microscopic examination using a polarizing filter. The background of the slides included fibroblasts, lymphocytes and other inflammatory cells. The finding within foreign-body giant cells of large groups of strongly birefringent, platelike crystals varying widely in size led to the conclusive cytologic diagnosis of intravenous talc granulomatosis.

Primary retroperitoneal seminoma diagnosed by fine needle aspiration biopsy. A case report.

A fine needle aspiration biopsy specimen of a retroperitoneal mass was submitted for cytologic evaluation. Malignant cells were found, and the cytologic appearance was consistent with seminoma although the clinical possibilities included lymphoma and adenocarcinoma of the pancreas. Cytologic features of the needle biopsy specimen included uniform neoplastic malignant cells with round nuclei and nucleoli and clear or pale-staining cytoplasm. The cells were found singly or in groups of two or three cells. Lymphocytes were intermingled with the neoplastic cells.

Cytopathology of thymoma.

From 1967 to 1981, 37 cases were diagnosed as thymoma by transthoracic fine needle aspiration biopsy. All were verified histologically, with no false-positive results. The various cytomorphologic patterns of thymoma are presented. All aspirates from the thymomas were reviewed and found to be composed of epithelial elements, with an admixture of lymphocytes in various proportions. There were 13 cases of lymphocytic predominance, 11 of epithelial-cell predominance, 4 of spindle-cell predominance, and 9 of mixed cell types. In the cytologic preparations the epithelial elements from different tumors exhibited different cytologic appearances and were tentatively subclassified into five types: small, intermediate, large, large pleomorphic and spindle shaped. The cytologic features of thymoma observed in aspiration biopsies are sufficiently distinctive from those of other anterior mediastinal tumors to be diagnostic. It appears feasible to investigate an anterior mediastinal mass with percutaneous fine needle aspiration for the purpose of establishing the diagnosis of thymoma prior to median sternotomy or thoracotomy.

Cytologic diagnosis of hepatocellular carcinoma by fine-needle aspiration biopsy.

From 1976 to June 1982, 237 patients with clinical suspicion of hepatic malignant disease underwent guided percutaneous fine-needle aspiration biopsy of the liver. Of these, 12 were diagnosed cytologically as "hepatocellular carcinoma" and this diagnosis was confirmed in the follow-up of all cases. On the basis of the cytomorphologic features observed in the aspirates, the tumor was subclassified into three types; well differentiated, pleomorphic large cell; and poorly differentiated. The various cytologic appearances of different types of hepatocellular carcinoma are presented and illustrated. Cytomorphologically, these three types of hepatocellular carcinoma were distinctly different and their cytomorphologic features were also sufficiently distinctive from those of secondary hepatic cancer to be diagnostic. Guided percutaneous fine-needle aspiration biopsy of the liver appears to be a definitive minimally invasive means of establishing the diagnosis of hepatocellular carcinoma, and promises to be a valuable diagnostic procedure for potentially resectable localized hepatocellular carcinoma.