Nasal asymmetry in unilateral cleft lip and palate.

OBJECTIVES: Comparison of nasal asymmetry between unilateral cleft lip and palate (UCLP) patients with and without nasal correction at primary repair. Assessment of the value of Symnose as a routine research tool. PARTICIPANTS: 75 ten-year-old UCLP patients who underwent primary lip repair by one of two techniques: classical Millard with primary nasal correction (n = 30) or modified Millard without nasal correction (n = 45). Control group of ten-year-old school children (n = 45). METHODS: Nasal asymmetry of participants was measured from facial photographs taken in two views: frontal and basal. The Symnose computer program was used to calculate asymmetry for three parameters: front perimeter (FP), base perimeter (BP) and nostrils (N). Total asymmetry was also calculated. Each image was traced on three separate occasions and a mean of the three measurements was calculated. RESULTS: BP, N and total asymmetry were significantly greater in UCLP patients without nasal correction compared to both controls and patients with correction (BP = 12.73% v 4.90% v 6.75%, N = 47.73% v 15.83% v 30.75%, total = 81.87% v 46.43% v 54.68%, p ≤ 0.001). FP asymmetry was significantly greater in controls than all UCLP patients (22.87% v. 18.18% and 15.07%, p = 0.001 and p = 0.008). BP measurements have a higher degree of repeatability than FP and N (Coefficient of repeatability = 5.99, 17.02 and 16.47, respectively). CONCLUSIONS: Primary nasal correction produces greater nasal symmetry during childhood from the basal view. Symnose is a simple method of objectively measuring asymmetry in UCLP, however improvements are required before it can be considered a useful research tool.

Expression of the putative stem cell marker Musashi-1 in Barrett's esophagus and esophageal adenocarcinoma.

The cancer stem cell theory states that cancers contain tumor-forming cells that have the ability to self-renew as well as give rise to cells that differentiate. Cancer stem cells have been identified in several solid tumors, but stem cells in normal human esophagus or in Barrett's esophagus or adenocarcinoma have not been reported. Musashi-1 is expressed by the crypt base columnar cells identified as intestinal stem cells. In other diseases of the gastrointestinal tract, local inflammation of the tunica mucosa may be an initiating factor of alteration of focal tissue 'niches,' where dormant stem cells locate. The present study investigated whether Musashi-1 is expressed in the esophagus and its relation to immune inflammation of the mucosa in Barrett's esophagus and esophageal adenocarcinoma. A total of 41 esophageal tissue specimens from 41 patients were studied. Of these, 15 were esophageal adenocarcinoma, 17 were Barrett's esophagus (10 intestinal metaplasia and 7 dysplasia), and 9 were normal squamous esophagus tissue specimens from patients without esophageal pathology. Immunohistochemistry was performed using antibodies to Musashi-1 and to a set of cell type-specific markers. A multiplexed tandem polymerase chain reaction method was used to measure the relative mRNA expression levels of Musashi-1 and the specific dendritic cell marker dendritic cell-specific intercellular molecule-3 (ICAM-3)-grabbing nonintegrin. Immunohistochemistry demonstrated the presence of small numbers of Musashi-1+ cells scattered in the connective tissue stroma and within the epithelium in cardiac-type glands in biopsies from patients without Barrett's esophagus. Musashi-1 expression was present in Barrett's intestinal metaplasia and in dysplastic Barrett's in which the majority of epithelial cells in individual glands expressed this antigen. Expression of Musashi-1 was highest in esophageal adenocarcinoma, where it was most intense in glands that displayed features of early stages of adenocarcinoma formation. In contrast, Musashi-1 staining level was weaker in glands that displayed features of advanced adenocarcinoma. Double immunostaining with proliferating cell nuclear antigen showed low proliferation in the vast majority of Musashi-1+ cells. Musashi-1 mRNA expression levels were significantly higher in esophageal adenocarcinoma than in normal esophagus or Barrett's esophagus tissues. Dendritic cell-specific intercellular molecule-3 (ICAM-3)-grabbing nonintegrin (DC-SIGN) mRNA expression levels were significantly increased in both Barrett's tissues and adenocarcinoma tissues. Expression of the putative stem cell marker Musashi-1 is absent in normal squamous epithelium, weak in esophageal cardiac-type glands and Barrett's esophagus, and markedly increased in adenocarcinoma, especially in glands displaying features of early cancer development. Musashi-1 expressing cells may be significant in the etiology of Barrett's esophagus and adenocarcinoma, and perhaps even a cell of origin for this disease. We speculate that immune inflammation occurring in Barrett's esophagus alters the mucosal microenvironment in a manner which is favorable to the activation of dormant stem cells.