Rapid mandible margins for intraoperative assessment.

OBJECTIVES: To determine the feasibility of a rapid method of processing mandible bone margins for intraoperative histopathologic examination and to assess the relative value of fine, coarse, and core specimens in assessing bone margins. STUDY DESIGN: Prospective histologic controlled study. SETTING: A tertiary level academic medical center histopathology laboratory. SUBJECTS AND METHODS: Multiple bone samples were collected from fresh (<12 hours post-mortem) human cadaveric mandible using a 1) standard 4mm otolaryngologic cutting drill bit 2) diamond drill bit and 3) cutting core biopsy trocar. The specimens were placed in one of three decalcifying solutions (Decal A, Calex, EDTA Decal) from 15 to 75 minutes or control (fixation in 10% formalin). After each designated decalcification time period, specimens were cryosectioned or paraffin embedded and subsequently reviewed by a head and neck surgical pathologist. The specimens were assessed for overall quality, adequacy of decalcification, soft tissue quality, marrow quality, and presence of artifact. RESULTS: Bone margin specimens collected with a 4mm burr and processed with EDTA Decal for 30 minutes yielded the highest quality histopathologic slides compared to the other methods in a similar time frame. The adequacy of decalcification directly impacted the quality of histopathologic assessment. CONCLUSIONS: Mandible bone margins can be rapidly and safely prepared and adequately evaluated with only 30 minutes of decalcification. This method may provide acceptable intraoperative assessment of bone margins in patients with tumors which involve or approximate bone. We plan to examine this model in a prospective clinical study of patients with cancer invading mandibular bone.

Modulation of the colonic epithelial cell responses and amelioration of inflammation by CD80 blockade in TNBS colitis.

Inflammatory bowel diseases (IBD) result from dysregulated immune responses to the luminal antigens initiated by the colonic epithelial cells (CEC) and propagated by activated CD4+ T cells. Biological therapies are being developed that suppress inflammation and promote epithelial homeostasis. Treatment with the CD80-competitive antagonist peptide (CD80-CAP) has been shown to suppress T cell responses in multiple disease models. Here we investigated the effect of the CD80-CAP on the CEC responses in experimental colitis. Balb/c mice induced with trinitrobenzene sulfonic acid (TNBS) colitis were administered CD80-CAP/control peptide/vehicle. Administration of the CD80-CAP decreased microscopic inflammation and restored the expression of TLR-2, 3, 4 and 5 mRNA in the CEC of colitis mice to physiological levels. Furthermore, the CD80-CAP treatment suppressed Th1 cytokines and enhanced Th2 responses by the CEC in colitis mice. In conclusion, CD80-CAP administration ameliorated TNBS colitis by reducing the inflammatory cell infiltration and modulating the CEC response potentially restoring mucosal tolerance.

Polymorphisms of xenobiotic metabolizing genes in oropharyngeal carcinoma.

OBJECTIVE: The objective was to determine the prevalence of the polymorphisms of the microsomal epoxide hydrolase (Ephx1), glutathione S-transferase mu1 (GSTM ), theta1 (GSTT1), and pi1 (GSTP1) genes in patients with oropharyngeal carcinoma. STUDY DESIGN: Gene polymorphisms in 137 patients with oropharyngeal carcinoma were determined by polymerase chain reaction and restriction enzyme digestion for xenobiotic metabolizing enzymes that have been implicated in the carcinogenesis of tobacco-related neoplasias and compared with a population sample of 99 persons. RESULTS: At Ephx1 (microsomal epoxide hydrolase) codon 113, an overrepresentation of the greater activity genotype (Tyr/Tyr) was observed for male ever-smokers alone, both male and female ever-smokers, female never-smokers alone, and in both male and female never-smokers, compared with a control population sample. At codon 139, Ephx1 showed no differences. There was an overrepresentation of homozygosity for the GSTT1 (glutathione S-transferase theta1) null allele [but not for the GSTM1 (glutathione S-transferase mu1) null allele] in ever-smokers, when compared with controls. Polymorphisms at the GSTP1 (glutathione S-transferase pi1) locus did not show differences versus controls, although in the never-smoker cancer sample there was a higher prevalence of the B/B genotype compared with ever-smokers. CONCLUSION: The Ephx1 codon 113 Tyr/Tyr variant, as well as homozygosity for the GSTT1 null allele, is associated with oropharyngeal carcinogenesis.