Dietary therapy can reverse esophageal subepithelial fibrosis in patients with eosinophilic esophagitis: a historical cohort.

BACKGROUND: Fibrosis of the esophageal lamina propria is a known complication of eosinophilic esophagitis (EoE). To date, therapy with topical corticosteroids has been shown to reverse esophageal fibrosis in some patients; however, there is little evidence to suggest that dietary therapy can also reverse it. Our aim was to examine whether dietary therapy alone can reverse esophageal fibrosis in children with EoE. METHODS: We performed a historical cohort study based on children with EoE who had esophageal fibrosis on pretreatment biopsies using trichrome staining. Post-treatment biopsies were analyzed for fibrosis reversal, and results were compared between patients treated with dietary restriction and those that received topical steroids. Clinical characteristics (age, symptoms, duration of symptoms prior to therapy, treatment type, and duration of therapy) were recorded. Histological markers (eosinophil numbers and eosinophilic degranulation in both epithelium and lamina propria, basal zone hyperplasia, and the presence of eosinophilic microabscesses in the epithelium) were examined by reviewing hematoxylin and eosin-stained biopsies and by immunohistochemical staining. These were examined as potential predictors for fibrosis reversal. RESULTS: Fibrosis resolved following both dietary restriction and topical steroids (3/17 and 5/9 patients respectively, P = 0.078). Post-treatment symptom resolution and decreased intraepithelial eosinophil numbers were found to be the only significant predictors of fibrosis resolution. CONCLUSIONS: Dietary restriction alone, similar to topical steroids, can reverse fibrosis in children with EoE.

Anti-lymphocyte therapy successfully controls late "cholestatic" rejection in pediatric liver transplant recipients.

Rejection is independently associated with liver graft loss in children. We report the successful rescue of grafts using ATG+/-OKT3 in late rejection associated with cholestasis. Retrospective chart review was performed after IRB approval. Between 2003 and 2010, 14 pediatric liver transplant recipients received anti-lymphocyte treatment for "cholestatic" rejection. Median age at transplantation was 12.7 yr (range 0.9-23.4), eight were boys, and immunosuppression was tacrolimus based. Median time from transplantation to rejection was five yr (range 1.1-10.5). Median peak total bilirubin was 11.1 mg/dL (range 1.4-18). All showed moderate to severe acute rejection and hepatocellular cholestasis on histology. ATG/OKT3 was started as first-line therapy in six and in the remaining eight as second-line therapy after failure of pulse steroids. Thirteen responded with normalization of aminotransferases and bilirubin, median time 16 wk (range 7-112); one non-adherent recipient has still not achieved normal graft function at last follow-up. Patient survival is 100%, with no re-transplantation and no post-transplant lymphoproliferative disease, median follow-up 2.9 yr (range 1.1-7.2). Cholestasis associated with acute rejection occurring late after liver transplantation may herald steroid resistance. First-line therapy with anti-lymphocyte preparations, prophylactic anti-microbial therapy, and close monitoring allow excellent rates of patient and graft survival.

Liver pathology in children with AIDS: a comparison between the South American and North American population.

Liver tissue from autopsies of twenty-nine cases of children with AIDS were collected from three major South America (S.4) pediatric hospitals. The hepatopathologic findings were classified in the same fashion as in a series of sixty-one children with AIDS from North America (NA): inflammation, non-specific, lymphoproliferative disorders, and giant cell transformation. By comparing both groups. we noted that the SA children were Younger at time of death consistent with a more rapid progression of the disease. Opportunistic infections varied with a higher prevalence of Cytomegalovirus (CMV) infection in SA children. The histopathologic features of CMV in the liter of SA children were associated with a conspicuous inflammation absent in the NA group. Finally, different non-specific hepatic changes were found in SA children, including one case of peliosis hepatis.

Expression of thyroid transcription factor-1, surfactant proteins, type I cell-associated antigen, and Clara cell secretory protein in pulmonary hypoplasia.

Pulmonary hypoplasia (PH) is a developmental abnormality characterized by diminished distal lung parenchyma. Recent studies have demonstrated that thyroid transcription factor 1 (TTF-1), a member of NKx2 family of homeodomain transcription factors, plays an important role in lung organogenesis and lung epithelial gene expression. In order to evaluate whether abnormal expression of TTF-1 contributes to the pathophysiology of PH, we studied the expression of TTF-1, as well as that of the surfactant proteins (SPs), Clara cell secretory protein (CCSP), and type I cell-associated antigen (T1 cell-Ag), in PH. Immunolocalization patterns of these proteins were evaluated in 15 cases of PH with different associated diseases and compared with those of 14 matched controls. Our study demonstrated that the concentration gradient of TTF-1 along the proximal-distal axis in normal fetal lung is disrupted in PH after 24 weeks gestational age, while the expression of the SPs, CCSP, and T1 cell-Ag seemed to be preserved. We conclude that a normal TTF-1 expression pattern might be crucial in the control of distal lung development. Failure to switch off expression of TTF-1 in PH of more than 24 weeks gestational age may be a final common pathway leading to PH associated with the disease processes investigated in this study.

Collision tumors in children: a review of the literature and presentation of a rare case of mesoblastic nephroma and neuroblastoma in an infant.

A mass made up of 2 distinct synchronous primary malignant tumors is a rare event in adults, and exceedingly so in children. Such lesions have been called collision tumors. Reported here is an infant who was found to have a collision tumor comprised of a neuroblastoma and a congenital mesoblastic nephroma, in contiguity, in the right kidney. This is the first report of a collision tumor in an infant. This also is the first report of a synchronous occurrence of a neuroblastoma and a congenital mesoblastic nephroma. The authors present this case and discuss the available literature.

Expression of thyroid transcription factor-1 in congenital cystic adenomatoid malformation of the lung.

Congenital cystic adenomatoid malformation (CCAM) is an abnormality of branching morphogenesis of the lung. CCAM types 1, 2, and 3 exhibit a cellular composition that is different from that of CCAM type 4 when evaluated with bronchiolar and alveolar cell markers. Thyroid transcription factor 1 (TTF-1) regulates early lung development. To evaluate the potential role of TTF-1 in the development of CCAM, TTF-1 expression in CCAM was compared to that of fetal lungs at varying gestational ages. Twenty-three CCAM cases (17 type 1, two type 2, two type 3, and two type 4) and 11 fetal lungs (3 pseudoglandular, 4 canalicular, and 4 terminal sac stages) were analyzed using a rabbit polyclonal antiserum to rat TTF-1. Nuclear staining for TTF-1 was observed in ciliated and nonciliated cells of the bronchial and bronchiolar epithelia and in cells lining the distal air spaces by 12 weeks gestational age. By mid-gestation, proximal bronchial cells were TTF-1 negative, except for the basal cells, while TTF-1 staining was maintained in distal bronchiolar and alveolar cells. TTF-1 expression decreased in both bronchial, bronchiolar, and alveolar epithelia with advancing gestational age and cytodifferentiation. At term, TTF-1 expression persisted in a few bronchial and bronchiolar basal cells and in all alveolar type II cells, whereas type I cells were negative. In CCAM, TTF-1 was detected in the nuclei of epithelial cells lining the cysts. TTF-1 was expressed in a majority of the bronchiolar-like epithelial cells of the cysts in CCAM types 1, 2, and 3, where almost 100% of the cells were TTF-1 positive. In contrast, TTF-1 expression in the alveolar-like epithelium of CCAM type 4 cysts was restricted to type II cells and only 30%-60% of the lining cells were TTF-1 positive. These results support the hypothesis that CCAM types 1, 2, and 3 reflect abnormalities in lung morphogenesis and differentiation that are distinct from those for CCAM type 4. The role played by TTF-1 in the development of CCAM, if any, is not clear.

Congenital cystic adenomatoid malformation of the lung (CCAM): evaluation of the cellular components.

Congenital cystic adenomatoid malformation of the lung (CCAM) is a rare congenital lesion whose pathogenesis is not well defined. It is generally accepted that the various types of CCAMs originate at different levels of the tracheobronchial tree. To further define the pathogenesis of CCAM, we evaluated the cellular composition of different CCAM types by immunohistochemistry. Twenty-two CCAMs (17 CCAM type 1, two type 2, one type 3, and two type 4) were collected. The cellular composition was determined using immunohistochemical stains for type I cell-associated antigen (T1 cell-Ag), surfactant proteins and surfactant protein precursors (SP-A, SP-B, proSP-B, and proSP-C), neuroendocrine cells (GRP), Clara cells (UP-1), and the adhesion molecule CD44v6, a glycoprotein thought to be involved in cell-matrix and cell-cell interactions. Eleven fetal lungs also were analyzed to compare cytodifferentiation of the epithelial-lined cysts of the different types of CCAM with the stages of normal lung development. Our results indicate that CCAM is caused by an arrest in lung development, and, on the basis of cytodifferentiation, two major subtypes can be distinguished. One subtype consisting of CCAM types 1, 2, and 3 that shows a bronchiolar type of epithelium and a second subtype, consisting of CCAM type 4, that has an acinar-alveolar type of epithelium. Our findings also suggest that these two subtypes may arise at different stages of the branching of the bronchopulmonary tree, the first at the pseudoglandular stage and the second at the saccular stage.

Immunohistochemical detection of Listeria antigens in the placenta in perinatal listeriosis.

Listeria monocytogenes, a worldwide pathogen, causes significant perinatal mortality and morbidity and has been implicated in spontaneous abortions, still-births, premature delivery, and neonatal sepsis, often with meningitis. Maternal symptoms are frequently minimal, and diagnosis is made only if the suspicion is high and diagnostic maternal blood or amniotic fluid cultures are performed. Because cultures are not routinely performed on spontaneously aborted fetuses, many authors feel that the true incidence of the disease may be underestimated. To date, the absence of a test to retrospectively diagnose Listeria infection has contributed to the lack of accurate estimates of the incidence of the disease. Seven cases in which immunohistochemical stains were used to confirm the diagnosis of placental listeriosis are described. All placentas showed the characteristic lesions with severe chorioamnionitis, numerous microabscesses, and focal necrotizing villitis. Immunohistochemical localization of Listeria antigen was made to the amnion (focally in areas with no inflammatory infiltrate), the abscesses, and the areas with villitis. In general, the antigen was extracellular and intracellular, predominantly within macrophages or the amnion epithelium. Listeria antigen was often found where definite identification of the organism was not possible on Brown-Hopps or Warthin-Starry stains. The immunohistochemical technique may therefore show an increase in sensitivity of detection of L monocytogenes compared with routine bacterial stains. Moreover, the ability to retrospectively evaluate placental specimens for evidence of this organism should permit the true incidence of perinatal listeriosis to be determined.