Liver fibrosis secondary to bile duct injury: correlation of Smad7 with TGF-beta and extracellular matrix proteins.

BACKGROUND: Liver fibrosis is the result of continuous liver injury stemming from different etiological factors. Bile duct injury induces an altered expression of TGF-beta, which has an important role in liver fibrosis because this cytokine induces the expression of target genes such as collagens, PAI-1, TIMPs, and others that lead to extracellular matrix deposition. Smad7 is the principal inhibitor that regulates the target gene transcription of the TGF-beta signaling. The aim of the study was to determine whether Smad7 mRNA expression correlates with the gene expression of TGF-beta, Col I, Col III, Col IV, or PAI-1 in liver fibrosis secondary to bile duct injury (BDI). RESULTS: Serum TGF-beta concentration was higher in BDI patients (39 296 pg/ml) than in liver donors (9008 pg/ml). Morphometric analysis of liver sections showed 41.85% of tissue contained fibrotic deposits in BDI patients. mRNA expression of Smad7, Col I, and PAI-1 was also significantly higher (P < 0.05) in patients with BDI than in controls. Smad7 mRNA expression correlated significantly with TGF-beta concentration, Col I and Col III expression, and the amount of fibrosis. CONCLUSION: We found augmented serum concentration of TGF-beta and an increase in the percentage of fibrotic tissue in the liver of BDI patients. Contrary to expected results, the 6-fold increase in Smad7 expression did not inhibit the expression of TGF-beta, collagens, and PAI-1. We also observed greater expression of Col I and Col III mRNA in BDI patients and significant correlations between their expression and TGF-beta concentration and Smad7 mRNA expression.

[Gastrointestinal stromal tumors in the pediatric population. Report of two cases and a review of the literature]. / Tumores estromales del tracto gastrointestinal en población pediátrica. Informe de dos casos y revisión de la literatura.

BACKGROUND: Gastrointestinal stromal tumors (GISTs) are uncommon mesenchymal tumors of the gastrointestinal (GI) tract that occur predominantly in adults. GISTs in pediatric patients are rare and not well characterized. We reviewed the presentation, diagnostic work-up, pathological specimens, and outcomes of two children with GIST that originated from the stomach. Literature pertaining to pediatric GISTs was also reviewed. CLINICAL CASES: Both patients presented with upper GI bleeding from a gastric tumor. The first patient was a 10-year-old male who underwent partial gastrectomy but had recurrence 26 years later requiring surgical exploration due to extensive infiltration into the surrounding organs; the tumor was not resected. The patient is currently being treated with imatinib mesylate. The second patient was a 12-year-old female who had a pedunculated mass originating from the stomach and requiring resection. She subsequently had a local recurrence 2 years later requiring partial gastrectomy. Adjuvant imatinib mesylate was recommended because of the large size of the tumor (8 cm). CONCLUSIONS: Pediatric GISTs represent a distinct subset of sarcomas with a strong predominance for females and gastric location, with 56 cases reported in the English-language literature.

Tumores estromales del tracto gastrointestinal en población pediátrica: informe de dos casos y revisión de la literatura / Gastrointestinal stromal tumors in the pediatric population: report of two cases and a review of the literature

Introducción: El tumor estromal del tracto gastrointestinal es una neoplasia rara que se presentan por lo general en la quinta a séptima década de la vida; en pacientes pediátricos es menos frecuente que en adultos y no está bien caracterizado. En esta descripción se evalúa presentación, diagnóstico clínicopatológico y evolución de dos niños con tumor estromal del tracto gastrointestinal originado en el estómago; también se revisa la literatura respecto a la experiencia mundial que se tiene con este tipo de tumor en la población pediátrica. Casos clínicos: Ambos pacientes iniciaron con hematemesis debido a un tumor gástrico. El primer paciente tenía 10 años de edad cuando se le practicó gastrectomía parcial; después de 26 años experimentó recurrencia local de la enfermedad, por lo que se le practicó laparotomía exploradora que mostró neoplasia con extensa infiltración a órganos vecinos. La neoplasia fue irresecable; se prescribió tratamiento con mesilato de imatinib. El segundo caso correspondió a una niña quien a los 12 años de edad presentó una masa unida a la pared gástrica por un pedículo, la cual fue resecada. Dos años después por recurrencia local se le practicó gastrectomía parcial. Se recomendó mesilato de imatinib como tratamiento adyuvante debido a que el tumor tenía 8 cm de diámetro mayor. Conclusiones: El tumor estromal del tracto gastrointestinal de presentación en la edad pediátrica representa un subgrupo distintivo de sarcomas que predomina en niñas y que por lo general afecta el estómago. En una revisión de la literatura solo se encontraron 56 casos de dicha neoplasia. El pronóstico es variable y heterogéneo. La resección completa de la neoplasia es indispensable y el tratamiento adyuvante con mesilato de imatinib se recomienda para los casos con alto riesgo.

BACKGROUND: Gastrointestinal stromal tumors (GISTs) are uncommon mesenchymal tumors of the gastrointestinal (GI) tract that occur predominantly in adults. GISTs in pediatric patients are rare and not well characterized. We reviewed the presentation, diagnostic work-up, pathological specimens, and outcomes of two children with GIST that originated from the stomach. Literature pertaining to pediatric GISTs was also reviewed. CLINICAL CASES: Both patients presented with upper GI bleeding from a gastric tumor. The first patient was a 10-year-old male who underwent partial gastrectomy but had recurrence 26 years later requiring surgical exploration due to extensive infiltration into the surrounding organs; the tumor was not resected. The patient is currently being treated with imatinib mesylate. The second patient was a 12-year-old female who had a pedunculated mass originating from the stomach and requiring resection. She subsequently had a local recurrence 2 years later requiring partial gastrectomy. Adjuvant imatinib mesylate was recommended because of the large size of the tumor (8 cm). CONCLUSIONS: Pediatric GISTs represent a distinct subset of sarcomas with a strong predominance for females and gastric location, with 56 cases reported in the English-language literature.

[Histological evaluation of hepatic fibrosis in patients with post surgical bile duct injury]. / Evaluación histológica de la fibrosis hepática en pacientes con lesión posquirúrgica de vías biliares.

BACKGROUND: Bile duct injuries after cholecystectomy can produce fibrous and collagen deposit tissue. Our objective was to evaluate the liver fibrosis measured in histological tissue in patients with bile duct injury after cholecystectomy. METHODS: Three normal liver biopsies and 21 from patients with bile duct injuries were studied. Group I: with three normal liver biopsies. Group II: with external abdominal fistula alone in six patients. Group III with complete bile duct obstruction in 15 patients. The surgical biliary enteric reconstructions were performed 8 weeks after bile duct injury in all cases. The fibrosis and collagen deposits were studied by Masson's trichrome and Sirius red stains and they were measured by a digital program. RESULTS: Group I showed 2 % of fibrosis tissue and 1% of collagen deposit and was considered as normal. Group II showed unexpected 1 fold more liver fibrosis and 9 fold more collagen deposit in extracellular matrix macromolecule (p < 0.05, Anova) against group I. Patients in group III, had fibrous tissue increase 43 folds more and 14 collagen folds more (p < 0.0001, Bonferroni's post hoc) versus group I. CONCLUSIONS: The patients in groups II and III showed liver fibrosis, being this more important in group III.