Lysosomal Acid Lipase Deficiency: Report of Five Cases across the Age Spectrum.

Lysosomal acid lipase (LAL) deficiency is an autosomal recessive lysosomal storage disorder caused by mutations in the LIPA gene that leads to premature organ damage and mortality. We present retrospective data from medical records of 5 Brazilian patients, showing the broad clinical spectrum of the disease.

Caracterização histopatológica da esofagite eosinofílica em crianças e adolescentes / Histological features of eosinophilic esophagitis in children and adolescents

ABSTRACT BACKGROUND: Eosinophilic esophagitis is an emerging disease featured by eosinophilic esophageal infiltrate not responsive to proton pump inhibitors. OBJECTIVE: To characterize histological features of children and adolescents with eosinophilic esophagitis. METHODS: Cross-sectional study in a tertiary hospital. Biopsies from each esophageal third from 14 patients (median age 7 years) with eosinophilic esophagitis were evaluated. Histological features evaluated included morphometry of esophageal epithelium, esophageal density (per high power field), extracellular eosinophilic granules, eosinophilic microabscesses, surface disposition of eosinophils, epithelial desquamation, peripapillary eosinophilia, basal layer hyperplasia and papillary elongation. RESULTS: Several patients presented a normal esophageal macroscopy in the upper digestive endoscopy (6, 42.8%), and the most common abnormality were vertical lines (7, 50%) and whitish spots over esophageal mucosa (7, 50%). Basal layer hyperplasia was observed in 88.8%, 100% e 80% of biopsies from proximal, middle and lower esophagus, respectively (P=0.22). Esophageal density ranges from 0 to more than 50 per hpf. Extracellular eosinophilic granules (70%-100%), surface disposition of eosinophils (60%-93%), epithelial desquamation (60%-100%), peripapillary eosinophilia (70%-80%) were common, but evenly distributed among each esophageal third. Just one patient did not present eosinophils in the lower third, four in the middle third and four in the upper esophageal third. CONCLUSION: In the absence of hypereosinophilia, other histological features are present in eosinophilic esophagitis and may contribute to diagnosis. Eosinophilic infiltrate is focal, therefore multiple biopsies are needed for diagnosis.

RESUMO CONTEXTO: Esofagite eosinofílica é uma doença emergente caracterizada por infiltrado eosinofílico esofágico não responsivo a inibidores de bomba de prótons. OBJETIVO: Caracterizar os achados histopatológicos de uma coorte de crianças e adolescentes com diagnóstico de esofagite eosinofílica. MÉTODOS: Estudo transversal conduzido em hospital terciário. Biópsias de terços proximal, médio e distal de 14 pacientes (idade mediana 7 anos) com diagnóstico de esofagite eosinofílica. Estudo morfométrico e variáveis histológicas analisadas em fragmentos de biópsias nos terços esofágicos: contagem de eosinófilos/CGA, grânulos eosinofílicos extracelulares, microabscessos eosinofílicos, disposição superficial de eosinófilos, descamação epitelial, eosinofilia peripapilar, hiperplasia da camada basal e alongamento de papilas. RESULTADOS: Vários pacientes apresentaram aspecto macroscópico normal da mucosa esofágica à endoscopia (6, 42.8%), e a anormalidade mais comumente observada foi linhas verticais (7, 50%) e exsudato branco (7, 50%). Hiperplasia da camada basal foi observada em 88,8%, 100% e 80% das biópsias do terço proximal, médio e distal respectivamente (P=0,22); contagem de eosinófilos nos terços variou de 0 a ≥50/CGA, grânulos eosinofílicos extracelulares (70%-100%), disposição superficial de eosinófilos (60%-93%), descamação epitelial (60%-100%), eosinofilia peripapilar (70%-80%), sem diferença estatística entre os terços esofágicos. Ausência de eosinofilia ocorreu raramente em terço distal (uma do distal, quatro do proximal, quatro do médio). CONCLUSÃO: Na ausência de hipereosinofilia, outros achados histopatológicos de inflamação eosinofílica estão presentes. A infiltração eosinofílica apresentou caráter focal, sugerindo-se a realização de múltiplas biópsias de diversos segmentos.

HISTOLOGICAL FEATURES OF EOSINOPHILIC ESOPHAGITIS IN CHILDREN AND ADOLESCENTS.

BACKGROUND: Eosinophilic esophagitis is an emerging disease featured by eosinophilic esophageal infiltrate not responsive to proton pump inhibitors. OBJECTIVE: To characterize histological features of children and adolescents with eosinophilic esophagitis. METHODS: Cross-sectional study in a tertiary hospital. Biopsies from each esophageal third from 14 patients (median age 7 years) with eosinophilic esophagitis were evaluated. Histological features evaluated included morphometry of esophageal epithelium, esophageal density (per high power field), extracellular eosinophilic granules, eosinophilic microabscesses, surface disposition of eosinophils, epithelial desquamation, peripapillary eosinophilia, basal layer hyperplasia and papillary elongation. RESULTS: Several patients presented a normal esophageal macroscopy in the upper digestive endoscopy (6, 42.8%), and the most common abnormality were vertical lines (7, 50%) and whitish spots over esophageal mucosa (7, 50%). Basal layer hyperplasia was observed in 88.8%, 100% e 80% of biopsies from proximal, middle and lower esophagus, respectively (P=0.22). Esophageal density ranges from 0 to more than 50 per hpf. Extracellular eosinophilic granules (70%-100%), surface disposition of eosinophils (60%-93%), epithelial desquamation (60%-100%), peripapillary eosinophilia (70%-80%) were common, but evenly distributed among each esophageal third. Just one patient did not present eosinophils in the lower third, four in the middle third and four in the upper esophageal third. CONCLUSION: In the absence of hypereosinophilia, other histological features are present in eosinophilic esophagitis and may contribute to diagnosis. Eosinophilic infiltrate is focal, therefore multiple biopsies are needed for diagnosis.

Diagnosis of Helicobacter pylori infection by means of reduced-dose ¹³C-urea breath test and early sampling of exhaled breath.

OBJECTIVE: The aim of this study was to evaluate the accuracy of reduced-dose ¹³C-urea breath test (¹³C-UBT) and early sampling of exhaled breath for the detection of Helicobacter pylori infection in children and adolescents. METHODS: Patients up to 20 years old that underwent upper gastrointestinal endoscopy with gastric biopsies were included. The ¹³C-UBT was performed after a 4-hour fasting period with 4 points of collection: baseline (T0), and at 10, 20, and 30 minutes (T10, T20, and T30) after ingestion of 25 mg ¹³C-urea diluted in 100 mL of apple juice. The infection status was defined through 3 invasive methods, and a patient was considered infected with a positive culture or concomitant positive histology and rapid urease test. The absence of infection was defined by all negative histology, rapid urease test, and culture. Analysis of exhaled breath samples was performed with an isotope-selective infrared spectrometer. A receiver-operating characteristic curve analysis was done to define cutoff delta over baseline (DOB) values. RESULTS: A total of 129 patients between the ages of 2.1 and 19 years (median 11.6 years; mean age ± standard deviation 11.5 ± 3.8 years; F:M 85:44) were included. The prevalence of infection was 41.1%. The sensitivity (S) and specificity (Sp) were at T10 (cutoff DOB 2.55‰), S 94.7% (95% confidence interval [CI] 90.9-98.5) and Sp 96.8% (95% CI 93.4-100); at T20 (DOB 2.5‰), S 96.2% (95% CI 92.9-99.5) and Sp 96.1% (95% CI 93.7-99.8); and at T30 (DOB 1.6‰), S 96.2% (95% CI 92.9-99.5) and Sp 94.7% (95% CI 90.8-98.6). CONCLUSIONS: Low-dose ¹³C-UBT with early sampling is accurate for diagnosing H pylori infection in children and adolescents.

Doença celíaca e constipação: uma manifestação clínica atípica e pouco frequente / Celiac disease and constipation: an uncommon atypical clinical manifestation / Enfermedad celíaca y constipación: una manifestación clínica atípica y poco frecuente

Relatar dois casos de doença celíaca (DC) com manifestação de constipação. DESCRIÇÃO DO CASO: Dois pacientes do sexo feminino, com 18 e 30 meses de idade, respectivamente, apresentando história de constipação crônica refratária ao tratamento. Como apresentavam concomitantemente baixo ganho ponderal e estatural, foi realizada investigação da função digestiva-absortiva, que resultou positiva para o anticorpo IgA antitransglutaminase tecidual. O diagnóstico de DC foi confirmado por biópsia de intestino delgado que revelou atrofia vilositária moderada/intensa e infiltrado linfocítico intraepitelial. Um mês após o início do tratamento com dieta isenta de glúten, ambas as pacientes passaram a apresentar fezes pastosas diariamente. COMENTÁRIOS: A DC pode se apresentar nas formas clássica, assintomática e atípica, em que manifestações isoladas como constipação podem retardar o diagnóstico.

To report two cases of patients with celiac disease (CD) whose main complaint was chronic constipation. CASE DESCRIPTION: Two girls, aged 18 and 30 months, had chronic constipation refractory to standard treatment. Both patients concomitantly evidenced low weight gain and short stature. The investigation of the digestive-absorptive function was positive for IgA antibodies against tissue transglutaminase. The diagnosis of CD was confirmed by a small bowel biopsy that showed moderate/severe villous atrophy and increased intraepithelial lymphocytic infiltration. One month after starting the dietary treatment with a gluten-free diet, both patients recovered from constipation, with the passage of soft stools daily. COMMENTS: CD may be presented in the classical, asymptomatic or atypical forms. In the latter form, isolated manifestations, surch as constipation, delay the diagnosis of the disease.

Relatar dos casos de enfermedad celíaca (EC) con manifestación de constipación. DESCRIPCIÓN DEL CASO: Dos pacientes del sexo femenino, con 18 y 30 meses de edad, respectivamente, presentando historia de constipación crónica refractaria al tratamiento. Como presentaban concomitantemente baja ganancia de peso ponderal y estatural, se realizó investigación de la función digestiva-absortiva, que resultó positiva para el anticuerpo IgA antitransglutaminasa tejidual. El diagnóstico de EC fue confirmado por biopsia de intestino delgado que reveló atrofia vellositaria moderada/intensa e infiltrado linfocítico intraepitelial. Un mes después del inicio del tratamiento con dieta exenta de gluten, ambas pacientes pasaron a presentar heces pastosas diariamente. COMENTARIOS: La EC puede presentarse en la forma clásica, asintomática y atípica, en que manifestaciones aisladas como constipación pueden retardar el diagnóstico.

Anti-tissue transglutaminase antibodies (IgA and IgG) in both Crohn´s disease and autoimmune diabetes.

OBJECTIVE: a strong association has been observed between celiac disease, generally its silent clinical form, and autoimmune disorders. A potential correlation with inflammatory bowel disease has also been suggested. Anti-tissue transglutaminase antibodies have been detected in Crohn´s disease. We investigated the prevalence of celiac disease in patients with autoimmune diabetes and in Crohn´s disease patients and also evaluated the correlation between anti-transglutaminase antibody positivity and the clinical status of these diseases. METHODS: anti-tissue transglutaminase and anti-endomysium antibodies were assessed by enzyme-linked immunosorbent assay and indirect immunofluorescence, respectively. Upper digestive endoscopy and duodenal biopsy were indicated for cases with positive serology. RESULTS: anti-transglutaminase antibodies were detected in five diabetic patients (prevalence of 11.1%), only one serum sample was positive for IgG isotypes. Nine of thirty-three patients with Crohn´s disease had low positive levels for IgA anti-transglutaminase. Antiendomysium antibodies were detected only in celiac patients. Celiac disease was confirmed in all diabetic patients submitted to duodenal biopsies who presented both anti-transglutaminase and anti-endomisyum antibodies positivity. In Crohn´s disease, its clinical status and the diagnosis of celiac disease were not associated with positiveanti-transglutaminase result. CONCLUSIONS: the prevalence of celiac disease was high in diabetic patients. Anti-tissue transglutaminase antibodies were sensitive and specific markers of celiac disease in this diabetic group, while these antibodies were of limited value for celiac disease screening in patients with Crohn´s disease.

Morphometrical and immunohistochemical study of intrahepatic bile ducts in biliary atresia.

BACKGROUND: Extrahepatic biliary atresia results from a progressive destruction of the bile ducts by an inflammatory fibrosing process which leads ultimately to cirrhosis of biliary type. The etiology of the disorder remains unknown. The histological features include cholestasis, ductular proliferation, eventual loss of intrahepatic bile ducts, and ducts with primitive embryonic shape (ductal plate malformation). PURPOSE: To examine the morphological changes of the biliary intrahepatic ducts, we aimed at investigating the cell proliferation and the diameter of the interlobular bile ducts in extrahepatic biliary atresia, and in normal liver children. METHODS: Liver samples from 35 patients with biliary atresia and 10 from control normal children were used. Immunoexpression of cytokeratin 19 was evaluated and a double-staining procedure was performed with cytokeratin 8/proliferating cell nuclear antigen. The stereological measurements of the intrahepatic bile ducts diameter were evaluated by a computerized system of image analysis. RESULTS: The patterns of intrahepatic cholangiopathy in biliary atresia were obstructive features (42.86%), paucity of intrahepatic bile ducts (20%), ductal plate malformation (28.57%), and ductal plate malformation associated with paucity of intrahepatic bile ducts (8.57%). The average external diameter of interlobular bile ducts in biliary atresia was smaller than that of the control infant livers. Among the four patterns of biliary atresia cholangiopathies, those associated with ductopenia showed the smallest bile duct diameter. There was a negative correlation between the bile duct to portal space ratio and the age of the child at the time of Kasai portoenterostomy. Only in biliary atresia are the bile duct cells stained with proliferating cell nuclear antigen. CONCLUSION: (i) In biliary atresia, both ductular metaplasia and ductular proliferation were observed; (ii) biliary atresia associated with ductopenia showed narrowing of interlobular ducts, probably as a consequence of degeneration with atrophy and fibrosis.

Gastric emptying evaluation in children with erosive gastroesophageal reflux disease.

BACKGROUND/AIMS: Delayed gastric emptying may be an important contributing factor to gastroesophageal reflux disease (GERD) in children, but there are limited data on its evaluation in children with erosive-GERD. This study aims to evaluate the gastric emptying of a solid meal in patients with erosive-GERD. METHODS: Nineteen patients (age range 8.79-17.9 years) with erosive esophagitis and 14 healthy controls (age range from 8.04 to 18.7 years) were compared. Esophagitis was graded according to Los Angeles classification. The gastric emptying was evaluated by (13)C-octanoic breath test, which was performed after a 344 kcal standardized solid test meal. Symptoms were evaluated using a standardized questionnaire. RESULTS: The two most prevalent symptoms were nausea and epigastric pain, which were reported by 12 (63.2%) patients. Irritable bowel syndrome was present in 26.3% (5/19). The median gastric emptying half-time in patients was 160 min (interquartile range [IQR] 140-174 min), which was not different from the controls' figure (median 157 min, IQR 143-170 min). Additionally, the lag time and the gastric emptying coefficient were not significantly different between the study groups. CONCLUSION: Delayed gastric emptying is not associated with erosive esophagitis in children with GERD, when compared to controls.

Detecção de Giardia intestinalis pelo teste de impressão duodenal e infecção por Helicobacter pylori em crianças e adolescentes com sintomas digestivos / Giardia intestinalis detected by biopsy imprint and Helicobacter pylori infection in dyspeptic children and adolescents

Objetivo: avaliar a relação entre a infecção por helicobacter pylori e a presença de giardia intestinalis, diagnosticada através do teste de impressão da mucosa duodenal em pacientes com dor abdominal. Material e métodos: foram avaliados prospectivamente 33 pacientes consecutivos com queixa de dor abdominal e que realizaram exame parasitológico de fezes; durante a endoscopia digestiva alta foram coletadas biópsias de duodeno para o teste de impressão e análise microscópica, e de mucosa do antro para pesquisa do H. pylori (teste rápido da urease e histologia). Resultados: o teste da impressão da mucosa duodenal foi positiva para giardia intestinalis em 9/33 pacientes (27,2%) e o H. pylori foi detectado em 21/33 (63,6%) pacientes, sendo 4/9 (44,4%) entre os pacientes infestados e 17/24 (70,8%) entre os não infestados por Giardia intestinalis. O exame parasitológico de fezes foi positivo em apenas 1/9 (11%) pacientes com o teste de impressão positivo; outros 3 pacientes apresentaram: ascaris lumbricoides, entamoeba coli e endolimax nana e a biópsia duodenal para giardia intestinalis foi positiva em 3/8 (37,5%). Conclusão: nossos resultados sugerem que não há associação entre parasitoses e infecção por Helicobacter pylori, sendo o teste de impressão da mucosa duodenal útil no diagnóstico da infestação por Giardia intestinalis durante investigação de pacientes com sintomas dispépticos submetidos à endoscopia digestiva. No entanto, são necessários mais estudos com maior amostragem.

Objective: to evaluate the relationship between helicobacter pylori infection and giardia intestinalis infestation, diagnosed by duodenal imprint test, in patients with abdominal pain. Material and methods: thirty three consecutive patients were prospectively evaluated by esophagogastroduodenoscopy and stool examination for ova and parasites. Duodenal biopsy was collected for imprint test and histological examination. H. pylori was diagnosed by histological examination of gastric antrum and rapid urease test. Results: duodenal imprint test was positive for giardia intestinalis in 9/33 patients (27.2%) and H. ylori was detected in 21/33 (63.6%) patients, 4/9 (44.4%) giardia intestinalis positive patients and 17/24 (70.8%) giardia intestinalis negative patients. Stool examination was positive in 1/9 (11%) patient with a positive duodenal imprint test, and another 3 patients presented ascaris lumbricoides, entamoeba coli e endolimax nana. Duodenal histology was positive for giardia intestinalis in 3/8 (37,5%). Conclusion: our results suggested that there is no association between giardiasis and Helicobacter pylori infection. Duodenal imprint test was useful to diagnose giardia intestinalis infestation in dyspeptic patients evaluated by esophagogastroduodenoscopy. Nevertheless, more studies with greater sampling are necessary.

Validation of a monoclonal stool antigen test for diagnosing Helicobacter pylori infection in young children.

BACKGROUND AND OBJECTIVE: The monoclonal stool antigen test for diagnosing Helicobacter pylori infection in children has been tested in developed countries, showing sensitivity and specificity higher than 90%. However, its accuracy in young children from developing countries is not well established. The aim of the study was to determine the accuracy of the monoclonal stool antigen test for diagnosing H pylori infection in children up to 7 years old. PATIENTS AND METHODS: Two hundred seventy-six patients (53.6% female; ages 0.35-6.99 years) were evaluated. Gold standard positive culture or positive histology and rapid urease tests were performed. The test (Amplified IDEIATM Hp StAR) was done according to the manufacturer's instructions. Results were expressed as optical density (OD) and an OD more than or equal to 0.190 was considered positive. Additionally, a receiver operating characteristic curve was used to find the best cutoff. RESULTS: The monoclonal stool antigen test for diagnosing H pylori infection showed 100% sensitivity (95% confidence interval [CI] 92.7%-100%) and 76.2% specificity (95% CI 70.1%-81.4%), considering the manufacturer's cutoff. After setting a new cutoff with the receiver operating characteristic curve (OD = 0.400), sensitivity remained 100% (95% CI 92.7%-100%), but the specificity improved to 97.7% (95% CI 94.7%-99%). At ages up to 2 years, sensitivity was 100% (95% CI 43.8%-100%) and specificity was 100% (95% CI 92.4%-100%); at ages 2 to 4 years, 100% (95% CI 80.6%-100%) and 97.6% (95% CI 96%-99.2%); at ages older than 4 years, 100% (95% CI 88.6%-100%) and 96.6% (95% CI 94.7%-98%), respectively. CONCLUSIONS: The monoclonal stool antigen test is accurate for diagnosing H pylori in children younger than 7 years old, but it must be locally validated in order to find the best cutoff for each population.

Síndrome megabexiga microcólon hipoperistaltismo intestinal: sobrevida até a adolescência / Megacystis-microcolon-intestinal hypoperistalsis syndrome: survival to adolescence

A síndrome megabexiga microcólon hipoperistaltismo intestinal (SMMHI) é uma doença rara, de provável herança genética, com prognóstico reservado, já no primeiro ano de vida. Relata-se um caso de SMMHI em criança do sexo feminino, atualmente com 16 anos de idade, com o objetivo de ressaltar o prognóstico favorável, não esperado, com sobrevida até a adolescência, de uma síndrome rara. Chama-se a atenção para a possibilidade de estabelecer o diagnóstico no período perinatal e para a importância de realizar o estudo urodinâmico.

Intraepithelial lymphocytes in duodenum from Brazilian adolescents with type 1 diabetes. Influence of Helicobacter pylori.

BACKGROUND: An increased number of intraepithelial lymphocytes (IELs) can be the only histological feature in early stages of celiac disease (CD). This is also presented in duodenum of patients with Helicobacter pylori-associated gastritis and in autoimmune diseases. Because CD is frequently associated with type 1 diabetes mellitus, we analyzed the density of IELs in the distal duodenum of non-celiac diabetic patients associated or not with H.pylori infection. METHODS: IEL density and the presence of H.pylori were determined in biopsies of the distal duodenum and gastric antrum and body obtained from Brazilian diabetic adolescents who were negative for anti-human tissue transglutaminase and anti-endomysial. The results were compared with the histological findings of gastric and duodenal biopsies obtained from non-diabetic older children and adolescents. RESULTS: H.pylori was detected in 33.3% of diabetic patients and in 56.7% of the control group. No association was observed between the presence of H.pylori and an increased lymphocyte density in the distal duodenum in either group. Diabetic patients presented a duodenal IEL density similar to that of the control group. Lymphocytic gastritis was not identified in any of the biopsies analyzed. CONCLUSIONS: The density of IELs in the distal duodenum of diabetic adolescents did not differ from that observed in older children and adolescents without this autoimmune disease. H.pylori infection, which is frequent among adolescents from developing countries, did not modify lymphocyte density in the distal duodenum in the absence of lymphocytic gastritis.

Osteossarcomas humanos de alto grau: imunoexpressão de p53, erb-2 e P-glicoproteína, e correlação com o parâmetro anaplasia / P-glycoprotein, erb2 and p53 expression in high-grade human osteosarcomas and their correlation with anaplasia

INTRODUÇÃO: Osteossarcoma (OS), o mais freqüente tumor primário maligno do osso, tem comportamento local agressivo e alto índice de disseminação sistêmica. Os eventos que permitem o crescimento e a disseminação tumoral ainda permanecem controversos. Os estudos sobre a carcinogênese e a progressão dessa neoplasia, com base na imunoexpressão de c-erb-B2, P-glicoproteína (P-gp) e p53, apresentam resultados conflitantes acerca do real valor prognóstico e suas correlações com parâmetros histológicos. A anaplasia, em neoplasias na infância, constitui parâmetro histológico de agressividade tumoral e quimiorresistência. Nos OS primários ou metastáticos, seu significado permanece controverso. Por outro lado, em outras neoplasias humanas, a expressão do c-erb-B2 relaciona-se com p53, grau nuclear e outros parâmetros de agressividade. OBJETIVO: Avaliar a imunoexpressão de p53, c-erb-B2 e P-gp em OS, correlacionando os parâmetros entre si e com a presença de anaplasia. MÉTODO: O estudo incluiu 96 biópsias pré-quimioterapia de pacientes com OS de alto grau, diagnosticados entre 1991 e 2000. A pesquisa imuno-histoquímica de p53, P-gp e c-erb-B2 foi feita pela técnica da estreptoavidina-biotina-peroxidase. Foram considerados positivos os casos onde havia imunoexpressão em 10 por cento ou mais das células neoplásicas. Somente colorações membranosa (para cerb-B2 e P-gp) e nuclear (para p53) foram consideradas positivas. Anaplasia foi definida como no tumor de Wilms, sendo considerada presente ou ausente. RESULTADOS: Anaplasia pôde ser avaliada em 82/96 casos, estando presente em 29 (35,36 por cento). Imunoexpressão de p53 foi detectada em 25 dos 60 casos (36,23 por cento); de P-gp, em 30 dos 73 casos (41,1 por cento); e de c-erb-B2, em 22 dos 55 casos (40 por cento). Os resultados demonstraram associação entre as imunoexpressões de c-erb-B2 e p53 (p = 0,042), p53 e o parâmetro anaplasia (p = 0,015), anaplasia e Pg (p = 0.034) CONCLUSÕES: A imunoexpressão...

BACKGROUND: Osteosarcomas (OS), the most frequent primary malignant bone tumors, have aggressive local behavior and high rate of metastatization. The events that allow tumor growth and dissemination are still controversial. The studies about carcinogenesis and tumor progression in this neoplasia, which are based on c-erb-B2, P-glycoprotein (P-gp) and p53 immunoexpression, show conflicting results as to the real prognostic value and its correlations with histological parameters. Anaplasia in childhood neoplasias is a histological parameter of tumor aggressiveness and chemoresistance. In primary or metastatic OS, its meaning remains controversial. On the other hand, in other human neoplasias, c-erb-B2 expression is associated with p53, nuclear grade and other aggressiveness parameters. OBJECTIVE: The aim of the present study was to evaluate p53, c-erb-B2 and P-gp immunoexpression in OS, correlating the parameters with the presence of anaplasia. METHODS: This study included 96 pre-chemotherapy biopsies in patients with high-grade OS diagnosed between 1991 and 2000. The immunohistochemical evaluation of p53 and c-erb-B2 was carried out with the streptavidin-biotin-peroxidase technique. Cases were considered positive when there was immunoexpression in 10 percent or more neoplastic cells. Only membrane staining (for c-erb-B2 and P-gp), and nuclear staining (for p53) were considered positive. Anaplasia was defined as Wilms' tumor, and considered present or absent. RESULTS: Anaplasia was present in 29 out of 82 cases (35.36 percent); p53 immunoexpression was detected in 25 out of 60 cases (36.23 percent); P-gp, in 30 out of 73 cases (41.1 percent); and c-erb-B2, in 22 out of 55 cases (40 percent). The results demonstrated an association between c-erb-B2 and p53 immunoexpression (p = 0.042), p53 and parameter of anaplasia (p = 0.015), anaplasia and P-gp (p = 0.034). CONCLUSIONS: The p53, c-erb-B2 and P-gp immunoexpression is relatively frequent in high-grade, metastic...

Gastric emptying of solids is slower in functional dyspepsia unrelated to Helicobacter pylori infection in female children and teenagers.

AIM: To evaluate gastric emptying of solids in children and adolescents with functional dyspepsia with and without Helicobacter pylori infection. PATIENTS AND METHODS: The study included 27 female patients (mean age 13.38 +/- 2.81 y) with functional dyspepsia according to Rome II criteria who were selected after upper gastrointestinal endoscopy found no major mucosal abnormality. Fragments were collected from the esophagus, gastric antrum, and gastric body for histological examination and rapid urease test. H. pylori infection was diagnosed according to the rapid urease test and histological appearance. The histological appearance of the gastric mucosa was evaluated according to modified Sydney criteria. A C-octanoic breath test was performed after a test meal (2 slices of toasted bread, 10 g margarine, and 1 egg with 100 microL of the tracer dipped in the yolk) with 13 points of air collection in 4 hours. RESULTS: Infection with H. pylori was observed in 12 of 27 patients (44.4%). The gastric emptying half-time was shorter in infected patients than in uninfected patients (mean +/- SD 153.4 +/- 20.0 min vs 179.2 +/- 32.2 min; P = 0.019), as was the lag phase (106.3 +/- 22.6 vs 126.6 +/- 22.7 min; P = 0.038). There was no relationship between gastric emptying (half-time and lag phase) and degree of histological abnormality. Vomiting and nausea were associated with slower gastric emptying in patients without H. pylori gastritis more often than in infected patients. CONCLUSIONS: The study suggests that delayed gastric emptying can play an important role in a subgroup of dyspeptic patients, particularly those without H. pylori infection who have nausea and vomiting.

High prevalence of celiac disease in Brazilian blood donor volunteers based on screening by IgA antitissue transglutaminase antibody.

OBJECTIVE: To study the prevalence of celiac disease among blood donor volunteers based on screening by IgA antitissue transglutaminase antibody, followed by a confirmatory small intestine biopsy. METHODS: The transversal study involved 3000 potential blood donors, residing in the city of Sao Paulo, Brazil. The participants were gender divided into 1500 men and 1500 women, with an average age 34.4+/-10.8 years, and included blood donor volunteers who could be turned down owing to anemia. All participants answered a questionnaire concerning the presence of diarrhea, constipation or abdominal pain during the 3 months before the study. Each participant with human recombinant IgA antitissue transglutaminase antibody level above 10 U/ml was invited to undergo a small intestine biopsy by means of an upper gastrointestinal endoscopy. The presence of villous atrophy and a positive antibody test were suggestive of possible celiac disease. RESULTS: Antitissue transglutaminase antibody was positive in 1.5% (45/3000) of the study population. Among the antibody-positive group, 21 (46.6%) agreed to have a biopsy performed, and within them the histological pattern of villous atrophy was confirmed in 66.7% (14/21). Consequently, the suggestive prevalence of celiac disease was at the minimum, one per 214 of the potential blood donor volunteers. A significant association was found between celiac disease and the symptoms of diarrhea, constipation and abdominal pain. CONCLUSIONS: The prevalence of celiac disease in Sao Paulo city is high and comparable to that observed in European countries. It is possible that in Brazil the prevalence of this disease had previously been underestimated.

[Analysis of clinicopathological, tumor cell proliferation and apoptosis parameters in adenocarcinoma of the gastric cardia]. / Estudo clínico-patológico, da proliferação celular e da apoptose no adenocarcinoma gástrico da cárdia.

BACKGROUND/AIMS: In view of the increased incidence of carcinoma of the cardia over recent years, this work had the aim of studying the clinicopathological aspects, cell proliferative and tumor apoptotic indices of this neoplasm, their interrelations and possible influences on the prognosis. MATERIAL AND METHODS: Forty cases of adenocarcinoma of the cardia were studied between 1988 and 2001, with a minimum clinical follow-up of 3 years. Patients were excluded if they had previous chemotherapy or radiotherapy treatment, presented early neoplasia, or died during the operations or for other reasons unrelated to cancer. Gender; age, Laurén and Ming histological type, staging, and the presence or absence of intestinal metaplasia, epithelial dysplasia and Helicobacter pylori in the adjacent mucosa were analyzed. The apoptotic index was evaluated via hematoxylin-eosin in the primary tumor. To analyze the cell proliferation tumor, PCNA was utilized. The immunohistochemical technique utilized was streptavidin-biotin-peroxidase. For the survival analysis, cases with distant metastasis upon diagnosis were excluded. For the statistical analysis, the Student t and Mann-Whitney tests, Kaplan-Meier curves and Cox regression model were utilized. RESULTS: The mean age was 61 years (median: 63). There was predominance of the male gender (72.5%), diffuse histological type (55%) and infiltrative histological type (72.5%), and the more advanced stages (III and IV: 67.5%). There was no association with intestinal metaplasia and/or H. pylori. No epithelial dysplasia was detected in adjacent mucosa in any of the cases. The mean apoptotic index was 7.05 in 10 high power fields and 11.40 in 500 cells (2.28%). The mean positivity to PCNA was 275.05 cells in ten high power fields and 409.33 in 500 cells (81.9%). There was a positive correlation between the cell proliferative and apoptotic indices. There was a positive correlation for intestinal histological type with PCNA and apoptotic indices, in 10 high power fields. The mean survival was 28.41 months. Age over 63 and apoptotic index over 7.05 showed a negative correlation with survival, in multivariate analysis. CONCLUSIONS: Adenocarcinoma of the cardia predominated in male adults of mean age 61 years, and the predominant type was diffuse in more advanced stages. There was a correlation between apoptosis and tumoral cell proliferation. Survival in cases of adenocarcinoma of the cardia is still low. Both age and apoptosis were independent prognostic factors in cancer of the cardia.

Aspectos funcionais, microbiológicos e morfológicos intestinais em crianças infectadas pelo vírus da imunodeficiência humana / Functional, microbiological and morphological intestinal findings among human immunodeficiency virus infected children

RACIONAL: O trato gastrointestinal é freqüentemente acometido nas crianças infectadas pelo vírus da imunodeficiência humana, com importantes repercussões no seu estado nutricional e sobrevida. A maioria dos estudos relacionados a esse tema foi desenvolvida com adultos, sendo menos investigado o problema nas crianças OBJETIVOS: Estudar aspectos digestivo-absortivos, microbiológicos e morfológicos intestinais em crianças infectadas pelo vírus da imunodeficiência humana MATERIAL E MÉTODOS: Onze crianças infectadas pelo vírus da imunodeficiência humana, menores de 13 anos, pertencentes às categorias clínicas A, B ou C, divididas em dois grupos: cinco pacientes com relato atual ou recente de diarréia e seis pacientes sem diarréia nos 30 dias que antecederam à inclusão no estudo. Investigação proposta: biopsia de intestino delgado e reto para análise morfológica e microbiológica, coprocultura, protoparasitológico de fezes, pesquisa de rotavírus, micobactérias e Cryptosporidium; teste da D-xilose RESULTADOS: Todos os pacientes testados (9/11) apresentavam má absorção da D-xilose (8,4-24,4 mg/dL). Os achados histopatológicos de intestino delgado foram inespecíficos, representados em sua maioria, por enteropatia grau I a II (6/10). Em todos os casos foi constatado aumento do infiltrado celular do córion. As alterações histopatológicas do reto também foram inespecíficas, com presença de aumento do infiltrado celular do córion. A pesquisa de microorganismos enteropatogênicos só foi positiva em dois casos, sendo identificado Mycobacterium avium intracellulare e Cryptosporidium nas fezes CONCLUSÕES: Demonstrou-se alta prevalência (100 por cento) de má absorção intestinal em crianças infectadas pelo vírus da imunodeficiência humana, com ou sem diarréia. Não foi possível estabelecer correlações quanto à presença de agentes enteropatogênicos, má absorção intestinal, alterações morfológicas intestinais e ocorrência ou não de diarréia. Não houve correlação...

BACKGROUD: Gastrointestinal tract disorders are frequent among human immunodeficiency virus infected children, with important repercussions on nutrition and survival. Most studies related to this subject were restricted to adults, being less investigated the problem in the children. AIMS: To study intestinal digestion, absorption, microbiological and morphological findings among human immunodeficiency virus infected children. MATERIAL AND METHODS: Eleven human immunodeficiency virus infected children under 13 years old, belonging to clinical categories A, B or C, separated in two groups: five patients with current or recent episode of diarrhea and six patients without diarrhea in the last 30 days preceding entering in study. Investigation proposed: microbiological and morphological analysis of small intestine and rectum biopsy; stool exams for bacterium, parasite, rotavirus, Mycobacterium species and Cryptosporidium; D-xylose test RESULTS: All tested subjects (9/11) had low D-xylose absorption (8,4 _ 24,4 mg d/L). Small intestinal mucosa histology findings were nonspecific, represented, in majority, of grade I/II enteropathy (6/10). Increased cellular infiltration of the chorion was observed in all specimens. Rectum histology alterations were also nonspecific, with chorion increased cellular infiltration. Mycobacterim avium intracellulare and Cryptosporidium were the solely microorganisms founded, both in stool CONCLUSIONS: Our study demonstrated high prevalence (100 percent) of intestinal malabsorption among human immunodeficiency virus infected children, despite the occurrence or not of diarrhea. It was not possible to establish relationships between the presence of microorganisms, intestinal malabsorption, intestinal morphologic findings and the occurrence or not of diarrhea. There was no correlation between D-xylose and intensity of villous atrophy.

Furazolidone-based triple therapy for H pylori gastritis in children.

AIM: To evaluate the furazolidone-based triple therapy in children with symptomatic H pylori gastritis. METHODS: A prospective and consecutive open trial was carried out. The study included 38 patients with upper digestive symptoms sufficiently severe to warrant endoscopic investigation. H pylori status was defined based both on histology and on positive (13)C-urea breath test. Drug regimen was a seven-day course of omeprazole, clarithromycin and furazolidone (100 mg, 200 mg if over 30 kg) twice daily. Eradication of H pylori was assessed two months after treatment by histology and (13)C -urea breath test. Further clinical evaluation was performed 7 d, 2 and 6 mo after the treatment. RESULTS: Thirty-eight patients (24 females, 14 males) were included. Their age ranged from 4 to 17.8 (mean 10.9 +/- 3.7) years. On intent-to-treat analysis (n = 38), the eradication rate of H pylori was 73.7% (95% CI, 65.2%-82%) whereas in per-protocol analysis (n = 33) it was 84.8% (95% CI, 78.5%-91%). All the patients with duodenal ulcer (n = 7) were successfully treated (100% vs 56.2% with antral nodularity). Side effects were reported in 26 patients (68.4%), mainly vomiting (14/26) and abdominal pain (n = 13). Successfully treated dyspeptic patients showed improvement in 78.9% of H pylori-negative patients after six months and in 50% of H pylori-positive patients after six months of treatment. CONCLUSION: Triple therapy with furazolidone achieves moderate efficacy in H pylori treatment. The eradication rate seems to be higher in patients with duodenal ulcer.

Estudo clínico-patológico, da proliferação celular e da apoptose no adenocarcinoma gástrico da cárdia / Analysis of clinicopathological, tumor cell proliferation and apoptosis parameters in adenocarcinoma of the gastric cardia / Analysis of clinicopathological, tumor cell proliferation and apoptosis parameters in adenocarcinoma of the gastric cardia

RACIONAL/OBJETIVO: Em vista do aumento na incidência do carcinoma da cárdia nos últimos anos, este trabalho visa estudar os aspectos clínico-patológicos, da proliferação celular e da apoptose tumorais, suas correlações e eventuais influências no seu prognóstico. MATERIAL E MÉTODO: Estudaram-se 40 doentes submetidos a gastrectomia total por carcinoma da cárdia, no período de 1988 a 2001, com seguimento clínico de no mínimo 3 anos. Excluíram-se aqueles com tratamento químio ou radioterápico prévio, neoplasia precoce, óbito no intra-operatório ou por outras causas não relacionadas ao câncer. Analisou-se sexo, idade, tipo histológico de Laurén, padrão de crescimento tumoral de Ming, estádio e presença ou ausência de metaplasia intestinal e/ou Helicobacter pylori na mucosa adjacente. O índice apoptótico foi avaliado por cortes histológicos corados pela hematoxilina-eosina. O índice de proliferação celular foi avaliado por meio da imunoexpressão ao PCNA, sendo a técnica imunoistoquímica utilizada a da estreptoavidina-biotina-peroxidase. Para análise da sobrevida, excluíram-se os casos com metástase à distância ao diagnóstico. Foram utilizados testes t de Student, de Mann-Whitney, curvas de Kaplan-Meier e modelo de regressão de Cox. O nível de significância adotado foi menor de 0,05. RESULTADOS: A idade média foi de 61 anos (mediana: 63); houve predomínio do sexo masculino (72,5 por cento), tipo histológico difuso (55 por cento) e infiltrativo (72,5 por cento) e de estádios mais avançados (III e IV: 67,5 por cento). Não houve associação com metaplasia intestinal e/ou H. pylori. O índice apoptótico médio foi de 7,05 em 10 campos consecutivos de grande aumento e de 11,40 em 500 células (2,28 por cento). A positividade média ao PCNA foi de 275,05 células em 10 campos consecutivos de grande aumento e de 409,33 em 500 células (81,9 por cento). Houve correlação positiva do tipo histológico intestinal com PCNA e com a apoptose em 10 campos consecutivos de grande aumento e de ...

BACKGROUND/AIMS: In view of the increased incidence of carcinoma of the cardia over recent years, this work had the aim of studying the clinicopathological aspects, cell proliferative and tumor apoptotic indices of this neoplasm, their interrelations and possible influences on the prognosis. MATERIAL AND METHODS: Forty cases of adenocarcinoma of the cardia were studied between 1988 and 2001, with a minimum clinical follow-up of 3 years. Patients were excluded if they had previous chemotherapy or radiotherapy treatment, presented early neoplasia, or died during the operations or for other reasons unrelated to cancer. Gender; age, Laurén and Ming histological type, staging, and the presence or absence of intestinal metaplasia, epithelial dysplasia and Helicobacter pylori in the adjacent mucosa were analyzed. The apoptotic index was evaluated via hematoxylin-eosin in the primary tumor. To analyze the cell proliferation tumor, PCNA was utilized. The immunohistochemical technique utilized was streptavidin-biotin-peroxidase. For the survival analysis, cases with distant metastasis upon diagnosis were excluded. For the statistical analysis, the Student t and Mann-Whitney tests, Kaplan-Meier curves and Cox regression model were utilized. RESULTS: The mean age was 61 years (median: 63). There was predominance of the male gender (72.5 percent), diffuse histological type (55 percent) and infiltrative histological type (72.5 percent), and the more advanced stages (III and IV: 67.5 percent). There was no association with intestinal metaplasia and/or H. pylori. No epithelial dysplasia was detected in adjacent mucosa in any of the cases. The mean apoptotic index was 7.05 in 10 high power fields and 11.40 in 500 cells (2.28 percent). The mean positivity to PCNA was 275.05 cells in ten high power fields and 409.33 in 500 cells (81.9 percent). There was a positive correlation between the cell proliferative and apoptotic indices. There was a positive correlation for intestinal ...

Urease activity does not reflect the degree of colonization by Helicobacter pylori in children.

BACKGROUND: Urea breath test is an accurate method for the diagnosis of Helicobacter pylori infection in children. This test could estimate the bacterial load by measuring the urease activity in gastric mucosa. The aim of the study was to correlate the result of 13C-urea breath test (13C-UBT) and histological estimative for bacterial colonization and severity of inflammatory infiltrate. METHODS: Forty-four patients (mean age 8.54 +/- 3.9 years) with dyspeptic symptoms were evaluated. Patients were evaluated through endoscopy and 13C-UBT. Helicobacter pylori infection was defined by histology, rapid urease test and 13C-UBT. Breath test results were expressed by delta over baseline (DOB) and urea hydrolysis rate (UHR). Test results were treated logarithmically for statistical analysis. RESULTS: There was a significant inverse correlation between age and Log DOB (-0.501, P= 0.0005), but there was no relationship between Log UHR and age (-0.148, P= 0.336). The study did not find correlation between the breath test result and histological grades for mononuclear infiltrate, neutrophilic infiltrate and bacterial density. CONCLUSION: The 13C-UBT does not estimate the severity of histological findings in children with Helicobacter pylori infection. The results of the breath test should be interpreted in a qualitative way.