The effects of methylprednisolone and halofuginone on preventing esophageal and hypopharyngeal fibrosis in delivered radiotherapy.

In this study, we assessed the effects of halofuginone and methylprednisolone on hypopharyngeal and esophageal stricture that can develop following radiation to the head and neck of rats. Rats were divided into four groups randomly and 18 Gy radiation was given to the head and neck regions of all rats except the control group. Group 1 (Control Group): No radiation or drugs were administered. Group 2 (Radiation Group): only radiation was applied without any drugs. Group 3 (Halofuginone Group): halofuginone 100 microg/kg per day was given intraperitoneally. Group 4 (Methylprednisolone Group): methylprednisolone 1 mg/kg per day was administered intramuscularly. In all groups, 90 days after application of radiation, sections of the proximal esophagus and hypopharynx were examined for fibrosis, fibroblast proliferation, vascularization, epithelial atypia, necrosis, polymorphonuclear leukocytes, mononuclear cells, and stenosis index by light microscope and the hydroxyproline levels were assessed biochemically. Fibrosis, epithelial atypia and hydroxyproline levels were found to be significantly higher in the radiation group compared to the control group (P < 0.05). We did not observe fibrosis in either the halofuginone or the control groups. Fibrosis was also significantly lower in the methylprednisolone group than the radiation group (P < 0.05). The differences of the stenosis index scores between the groups were not statistically significant (P < 0.05). Vascularization was similar in all groups. We think that especially halofuginone is a drug that can be used safely to prevent fibrosis due to radiotherapy, but further studies are needed.

Evaluation of bcl-2, bax and c-erbB-2 Levels in Chronic Otitis Patients with or without Cholesteatoma.

OBJECTIVE: The aim of this study was to evaluate bcl-2, bax, and c-erbB-2 expressions in primary and secondary acquired cholesteatoma and to indicate the role of apoptosis and accompanying increased cellular proliferation in the pathogenesis of cholesteatoma. METHODS: Samples obtained from the skin of the external ear canal (EEC) of patients operated for chronic otitis media (COM) without cholesteatoma constituted Group 1; samples from the EEC skin of patients in Group 3 operated for COM with cholesteatoma and from the EEC skin of patients in Group 4 constituted Group 2; samples obtained from the cholesteatoma matrix of patients operated for COM with primary acquired cholesteatoma constituted Group 3; and samples obtained from the cholesteatoma matrix of patients operated for COM with secondary acquired cholesteatoma constituted Group 4. The assessment of the positive cell ratio was based on the presence of the following findings and was semiquantitatively classified into four groups: 0, no staining; + cell staining (weak positive staining: 1%-33%); ++ cell staining (moderately positive staining: 34%-66%); and +++ cell staining (strong positive staining: 67%-100%). RESULTS: Comparison of the staining scores of bcl-2, bax, and c-erbB-2 revealed a statistically insignificant difference in the staining of samples obtained from the EEC skin (p>0.05). Decreased bcl-2 expression and increased bax and c-erbB-2 expressions were determined in primary and secondary acquired cholesteatoma epithelium compared with the EEC skin of patients operated for COM with or without cholesteatoma, and the differences were found to be statistically significant (p<0.05). CONCLUSION: In acquired cholesteatoma epithelium, the finding of decreased bcl-2 expression as well as increased bax and c-erbB-2 expressions compared with the EEC skin is an indicator of the increase in both cellular proliferation and apoptosis.