Immunological and classical subtypes of oral premalignant lesions.

Oral squamous cell carcinoma (OSCC) is a major cause of cancer-associated morbidity and mortality and may develop from oral premalignant lesions (OPL). An improved molecular classification of OPL may help refining prevention strategies. We identified two main OPL gene-expression subtypes, named immunological and classical, in 86 OPL (discovery dataset). A gene expression-based score was then developed to classify OPL samples from three independent datasets, including 17 (GSE30784),13 (GSE10174) and 15 (GSE85195) OPLs, into either one of the two gene-expression subtypes. Using the single sample gene set enrichment analysis, enrichment scores for immune-related pathways were different between the two OPL subtypes. In OPL from the discovery set, loss of heterozygosities (LOH) at 3p14, 17p13, TP53, 9p21 and 8p22 and miRNA gene expression profiles were analyzed. Deconvolution of the immune infiltrate was performed using the Microenvironment Cell Populations-counter tool. A multivariate analysis revealed that decreased miRNA-142-5p expression (P = 0.0484) and lower T-cell, monocytic and myeloid dendritic cells (MDC) immune infiltration (T-cells, P = 0.0196; CD8 T cells, P = 0.0129; MDC, P = 0.0481; and monocytes, P = 0.0212) were associated with oral cancer development in the immunological subtype only. In contrast, LOH at 3p14 (P = 0.0241), 17p13 (P = 0.0348) and TP53 (P = 0.004) were associated with oral cancer development in the classical subtype only. In conclusion, we identified 2 subtypes of OPLs, namely immune and classical, which may benefit from different and specific personalized prevention interventions.

Treatment of Velopharyngeal Insufficiency: Fifteen-Year Experience at the University of Florida.

INTRODUCTION: A 15-year experience treating velopharyngeal insufficiency at the University of Florida is presented. After diagnostic speech evaluation, preoperative videofluoroscopy was the primary method used to evaluate the function of the velopharyngeal port. METHODS: Chart reviews of all patients with velopharyngeal insufficiency, including patients with failed palatal cleft surgery, submucous cleft palate, and noncleft palate who met study criteria were included. RESULTS: Overall success of treatment was 92%. Results are described by subgroups for further clarification. CONCLUSION: Selection of surgical procedure based on preoperative evaluation of velopharyngeal function and anatomy leads to a high rate of success.

Longitudinal study of growth of children with unilateral cleft lip and palate: 2 to 10 years of age.

Objective : To study the growth of children with complete unilateral cleft lip and palate (UCLP) from 2 to 10 years of age and to assess whether growth varied from that of children without UCLP (typical children). Design : Physical growth was one of the outcome measures of a National Institutes of Health-sponsored longitudinal, prospective clinical trial conducted by the University of Florida and the University of São Paulo. Setting : Hospital of Rehabilitation of Craniofacial Anomalies, University of São Paulo (HRAC-USP), Bauru, Brazil. Main Outcome Measures : Height and weight were prospectively measured for 360 healthy children with UCLP who were nonsyndromic, belonged to median socioeconomic status, and received health care at HRAC-USP. To compare growth of children with UCLP to that of typical children, growth curves for UCLP were developed and compared with World Health Organization curves for 2006 and 2007, which were used as reference for typical children. Third-degree polynomials were used to explain the relationship of length and weight with age. Confidence limits of 95% were used for the mean curve using the statistic Z ~ N (0,1). Results : Children with UCLP from 2 to 10 years old presented height and weight growth curves similar to those of typical children for both genders. Conclusion : Children with UCLP from 2 to 10 years old presented physical growth similar to that of typical children.

Otologic and audiologic outcomes with the Furlow and von Langenbeck with intravelar veloplasty palatoplasties in unilateral cleft lip and palate.

OBJECTIVE: Cleft palate increases the risk of chronic middle ear disease and hearing loss. The goal of this report was to determine which of two palate surgeries and which timing of palate surgery were associated with better otologic and audiologic outcomes in children with unilateral cleft lip and palate at 5 to 6 years of age. DESIGN: Subjects were randomly assigned to the von Langenbeck with intravelar veloplasty or Furlow palate repair, to palate surgery at 9 to 12 months or 15 to 18 months of age, and to the Spina or Millard lip repair. SETTING: Centralized, tertiary care craniofacial treatment center. PATIENTS: A total of 673 infants with unilateral cleft lip and palate. INTERVENTIONS: Palate and lip were repaired using established techniques. Serial otoscopic and audiometric evaluations were performed. MAIN OUTCOME MEASURES: Hearing and otoscopic findings at 5 to 6 years old. RESULTS: There were 370 children available for analysis. Hearing and need for tympanostomy tube placement did not differ by palatoplasty, age at palatoplasty, cheiloplasty, or surgeon. Risk of developing cholesteatoma or perforation was higher with Millard cheiloplasty (odds ratio  =  5.1, 95% confidence interval  =  1.44 to 18.11, p  =  .012). Type and age at palatoplasty were not significantly associated with either the rate of developing these sequelae or the rate of achieving bilaterally normal hearing and ear examinations. CONCLUSIONS: Type of palatoplasty did not influence otologic and audiologic outcomes in 5- to 6-year-olds with unilateral cleft lip and palate. The potential influence of lip repair on otologic outcomes warrants further investigation.

Prospective clinical trial comparing outcome measures between Furlow and von Langenbeck Palatoplasties for UCLP.

The goal of this prospective randomized clinical trial was to compare 2 cohorts of standardized cleft patients with regard to functional speech outcome and the presence or absence of palatal fistulae. The 2 cohorts are randomized to undergo either a conventional von Langenbeck repair with intravelar velarplasty or the double-opposing Z-plasty Furlow procedure. A prospective 2 × 2 × 2 factorial clinical trial was used in which each subject was randomly assigned to 1 of 8 different groups: 1 of 2 different lip repairs (Spina vs. Millard), 1 of 2 different palatal repair (von Langenbeck vs. Furlow), and 1 of 2 different ages at time of palatal surgery (9-12 months vs. 15-18 months). All surgeries were performed by the same 4 surgeons. A cul-de-sac test of hypernasality and a mirror test of nasal air emission were selected as primary outcome measures for velopharyngeal function. Both a surgeon and speech pathologist examined patients for the presence of palatal fistulae. In this study, the Furlow double-opposing Z-palatoplasty resulted in significantly better velopharyngeal function for speech than the von Langenbeck procedure as determined by the perceptual cul-de-sac test of hypernasality. Fistula occurrence was significantly higher for the Furlow procedure than for the von Langenbeck. Fistulas were more likely to occur in patients with wider clefts and when relaxing incisions were not used.

Longitudinal study of growth of children with unilateral cleft-lip palate from birth to two years of age.

OBJECTIVE: To study the growth of children with complete unilateral cleft lip and palate (UCLP) from birth to 2 years of age and to construct specific UCLP growth curves. DESIGN: Physical growth was a secondary outcome measure of a National Institutes of Health-sponsored longitudinal, prospective clinical trial involving the University of Florida (United States) and the University of São Paulo (Brazil). PATIENTS: Six hundred twenty-seven children with UCLP, nonsyndromic, both genders. METHODS: Length, weight, and head circumference were prospectively measured for a group of children enrolled in a clinical trial. Median growth curves for the three parameters (length, weight, head circumference) were performed and compared with the median for the National Center for Health Statistics (NCHS) curves. The median values for length, weight, and head circumference at birth and 6, 12, 18, and 24 months of age were plotted against NCHS median values and statistically compared at birth and 24 months. SETTING: Hospital de Reabilitação de Anomalias Craniofaciais, Universidade de São Paulo, Bauru, Brazil (HRAC-USP). RESULTS: At birth, children of both genders with UCLP presented with smaller body dimensions in relation to NCHS median values, but the results suggest a catch-up growth for length, weight, and head circumference for girls and for weight (to some degree) and head circumference for boys. CONCLUSIONS: Weight was the most compromised parameter for both genders, followed by length and then head circumference. There was no evidence of short stature. This study established growth curves for children with UCLP.

Prosthetic management of pharyngeal flap-related snoring.

OBJECTIVE: The obturating pharyngeal flap used in correcting velopharyngeal insufficiency has been implicated in creating difficulty in nasal breathing for some patients and/or in causing hyponasal speech, obstructive sleep apnea, and snoring. This is a case report of an individually designed removable prosthesis that positions an acrylic tube through each port lateral to the pharyngeal flap, with the goal of preventing the collapse of the ports during sleep and the consequent snoring. DESIGN: The acrylic tubes maintain an opening through both lateral ports preventing the soft tissues of the lateral walls from vibrating against the pharyngeal flap (causing the snoring sound) and allowing nasal breathing. RESULTS: The acrylic tubes effectively eliminated the patient's problem of snoring. CONCLUSIONS: This case study demonstrates that snoring associated with a pharyngeal flap can be controlled prosthetically by maintaining an opening through the two lateral ports, preventing the soft tissues of the walls of the lateral ports from vibrating against the flap.

Effect of nasal decongestion on nasalance measures.

OBJECTIVE: The purpose of this study was to evaluate the effect of nasal decongestant on nasalance scores for a group of 100 individuals. PARTICIPANTS: Forty-one subjects with hypernasality and 59 subjects without hypernasality underwent nasometric assessment at the Hospital for Rehabilitation of Craniofacial Anomalies, University of São Paulo, Bauru, Brazil. DESIGN: Nasalance scores were obtained for each subject before the application of a nasal decongestant and again 10 minutes after subjects received a topical nasal decongestant applied into both nostrils. RESULTS: The nasalance scores obtained after the application of the nasal decongestant were significantly higher than those obtained before the decongestant. CONCLUSIONS: Nasal decongestion had a small but statistically significant effect on nasalance scores, suggesting that in some individuals, nasal congestion should be a variable of concern when using the Nasometer. Both nasal congestion (i.e., due to nasal rhinitis) and the effects of nasal decongestant sprays may influence Nasometer test results. Interpretation of nasalance scores, therefore, should be done carefully. Furthermore, nasometry, with and without nasal decongestant, can be a valuable clinical tool for screening anterior nasal obstruction, helping to isolate obstruction due to nasal congestion from structural obstruction in the nasal cavities.

Immediate and sustained changes in tongue movement with an experimental palatal "fistula": a case study.

OBJECTIVE: To determine the immediate and longer-term effect(s) on tongue movement following the placement of an experimental opening through a palatal obturator (replicate of subject's prosthesis) worn by an adult male with an unrepaired cleft of the hard and soft palate. METHODS: Tongue movements associated with an anterior experimental opening of 20 mm(2) were examined under three conditions: a control condition in which the subject wore the experimental obturator completely occluded, a condition immediately after drilling the experimental openings through the obturator, and a condition after 5 days in which the subject wore the experimental obturator with the experimental opening. An Electromagnetic Articulograph was used for obtaining tongue movements during speech. RESULTS: The findings partly revealed that the immediate introduction of a perturbation to the speech system (experimental fistula) had a temporary effect on tongue movement. After sustained perturbation (for 5 days), the system normalized (going back toward control condition's behavior). Perceptual data were consistent with kinematic tongue movement direction in most of the cases. CONCLUSIONS: Although the immediate response can be interpreted as indicative of the subject's attempts to move the tongue toward the opening to compensate for air loss, the findings following a sustained perturbation indicate that with time, other physiological adjustments (such as respiratory adjustments, for example) may help reestablish the requirements of a pressure-regulating system.

Intraoral air pressure discrimination under conditions of experimental velopharyngeal insufficiency.

OBJECTIVE: This study assessed a single subject's ability to detect the difference limen (DLs) for his self-generated intraoral air pressure while his oral and nasal cavities were experimentally coupled. METHOD: The subject, a 46-year-old man, uses a speech bulb prosthesis to cover an unrepaired cleft of his hard and soft palates. The subject's oral and nasal cavities were experimentally coupled by drilling different size holes through the speech-bulb component of the prosthesis to approximate conditions of velopharyngeal insufficiency. There were four hole-size conditions (10, 15, 20, and 30 mm(2)), a no-prosthesis condition, and pre- and postbaseline conditions with the prosthesis intact. The subject blew into a tube connected to a pressure transducer and was presented with a series of paired pressure loads. The first pressure load of each pair was the referent (1, 3, or 5 cm H(2)O), and the second was a preselected comparator load of a different amount. The subject blew into the tube with sufficient force to center the voltage meter's needle at the zero mark. The subject then reported whether the second pressure load required more, less, or equal breath pressure, compared with the referent pressure load of that pair. RESULTS: Size of the hole coupling the oral/nasal cavities did not significantly affect the subject's difference limen. CONCLUSION: Experimental coupling of the oral/nasal cavities did not affect this subject's ability to detect differences in his self-generated intraoral air pressure.

Evaluation and treatment of velopharyngeal insufficiency: the University of Florida experience.

This retrospective study spans the years 1988 to 2000 and looks specifically at the treatment procedures and outcomes for the correction of velopharyngeal insufficiency (VPI). Ninety-eight patients underwent preoperative assessment by speech pathologists that included perceptual speech evaluation, videofluoroscopy, and, for some, nasendoscopy. Based on this evaluation protocol, a specific surgical procedure was chosen to serve the patients' needs. The four procedures of choice were the palatal pushback with a pharyngeal flap lining, sphincter pharyngoplasty, a superiorly based obturating pharyngeal flap, and Furlow palatoplasty. The criteria for selecting these procedures are reviewed. The results revealed VPI resolution and the establishment of normal nonnasal speech in more than 95% of the 75 patients for whom outcomes were determined. This study reiterates the importance of thorough preoperative evaluation and the individualization of the secondary corrective procedure.