Eosinophilic esophagitis (EE) is an emerging disease caused by dense infiltration of the esophageal epithelium by eosinophilic leucocytes. It is originated from local hypersensitivity to food or airborne allergens. Although the physiopathologic mechanisms of the illness have not been fully discovered, EE is a loss of immunologic tolerance by the esophagus, meaning that it should be considered as an active immunologic organ. In our study, we investigated the immunologic capacity of the epithelium using immunohistochemistry and stereology, to determine the cellular density of eosinophils, T and B lymphocytes, Langerhans cells, mast cells, and cells manufacturing immunoglobulin E in endoscopic biopsies of patients with EE (taken before and after topical treatment with fluticasone propionate) compared with normal individuals and patients suffering from gastroesophageal reflux disease (GERD). We have observed that the density of eosinophils in EE is 300 times greater than in normal conditions and it is only in this disease where eosinophils show signs of activation and degranulation (positivity to major basic protein immunostaining). The number of T intraepithelial lymphocytes also significantly rose in EE, compared with other entities, where CD8 cells were predominant. However, the human esophagus is deficient in B lymphocytes and we only found intraepithelial plasma cells that excreted immunoglobulin E in EE. Under normal conditions mast cells exist in the thickness of the epithelium that are slightly higher in GERD and multiply in density by 17 in EE. Langerhans cells did not show any significant variation in density under the different tested conditions. After topical treatment with steroids, the density of the different cell components fell to similar levels to GERD. Using our study, we can conclude that the human esophagus may contribute to the development of local immunologic responses as it contains all the necessary cell components. EE represents growth of this esophageal capacity and its pathogeny could respond to mixed cellular and humoral mechanisms.

Background KRAS mutations in colorectal cancer primary tumors predict resistance to anti-Epidermal Growth Factor Receptor (EGFR) monoclonal antibody therapy in patients with metastatic colorectal cancer, and thus represent a true indicator of EGFR pathway activation status.Methodology/Principal Findings KRAS mutations were retrospectively studied using polymerase chain reactions and subsequent sequencing of codons 12 and 13 (exon 2) in 110 patients with metastatic colorectal tumors. These studies were performed using tissue samples from both the primary tumor and their related metastases (93 liver, 84%; 17 lung, 16%). All patients received adjuvant 5-Fluorouracil-based polychemotherapy after resection of metastases. None received anti-EGFR therapy. Mutations in KRAS were observed in 37 (34%) of primary tumors and in 40 (36%) of related metastases, yielding a 94% level of concordance (kappa index 0.86). Patients with primary tumors possessing KRAS mutations had a shorter disease-free survival period after metastasis resection (12.0 vs 18.0 months; P = 0.035) than those who did not. A higher percentage of KRAS mutations was detected in primary tumors of patiens with lung metastases than in patients with liver metastases (59% vs 32%; p = 0.054). To further evaluate this finding we analyzed 120 additional patients with unresectable metastatic colorectal cancer who previously had their primary tumors evaluated for KRAS mutational status for clinical purposes. Separately, the analysis of these 120 patients showed a tendency towards a higher degree of KRAS mutations in primary tumors of patients with lung metastases, although it did not reach statistical significance. Taken together the group of 230 patients showed that KRAS was mutated significantly more often in the primary tumors of patients with lung metastases (57% vs 35%; P = 0.006).Conclusions/SignificanceOur results suggest a role for KRAS mutations in the propensity of primary colorectal tumors to metastasize to the lung.

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Combination therapy with PEG-IFN-alpha2b and ribavirin treatment was effective in children with chronic hepatitis C. Virologic status at week 12 identified future responders and nonresponders. PEG-IFN-alpha2b and ribavirin were reasonably well tolerated, with no unexpected or permanent adverse effects. Further studies are needed to identify the optimum treatment regimen for this patient population.

Severe bile salt export pump (BSEP) deficiency is a hereditary cholestatic condition that starts in infancy and leads to end-stage liver disease. Three children who underwent orthotopic liver transplantation for severe BSEP deficiency had post-transplantation episodes of cholestatic dysfunction that mimicked the original disease. Remission of all episodes was achieved by intensifying the immunosuppressive regimen. The phenotypic recurrence of the disease correlated with the presence of circulating high-titer antibodies against BSEP that inhibit transport by BSEP in vitro. When administered to rats, these antibodies targeted the bile canaliculi and impaired bile acid secretion.