Malocclusion in the primary dentition in children with and without deformational plagiocephaly.

OBJECTIVES: Asymmetries of the jaw and orthodontic abnormalities are suspected as long-term consequences of positional cranial deformity. But only few data exist on this issue. As plagiocephaly is a common problem in infancy, potential functional impairments should be investigated to initiate appropriate measures if necessary. The aim of our study was to compare the orthodontic situation in primary dentition of children with positional plagiocephaly and children without cranial deformities. MATERIAL AND METHODS: Fifty children treated by helmet therapy for plagiocephaly and 50 non-affected children (age 1.98-5.69 years) were examined in a cross-sectional study. Orthodontic parameters of all dimensions were assessed and analyzed. RESULTS: Children of the plagiocephalic group showed more often orthodontic alterations compared to the others. Especially the frequencies of a class II malocclusion (36 vs. 14 %), an edge-to edge bite (28 vs. 12 %), and deviations of the midline (38 vs. 16 %) were conspicuous. However, none of the differences was significant (p > 0.003). Of all observed mandibular asymmetries, 69 % appeared as a shift to the contralateral side of the former flattened occipital region. CONCLUSION: Positional head deformity might be associated in some cases with a higher prevalence of occlusal abnormalities in primary dentition. CLINICAL RELEVANCE: Positional plagiocephaly interfaces medicine and dentistry. As it is a common disorder, this etiology has to be considered in the prevention and therapy of malocclusion.

Evaluation of a biomarker based blood test for monitoring surgical resection of oral squamous cell carcinomas.

INTRODUCTION: The potential use of determination of biomarkers in blood for the monitoring of surgical removal of oral squamous cell carcinomas (OSCC) was evaluated using the epitope detection in monocytes (EDIM) technology. MATERIALS AND METHODS: In tumor specimen, elevated Apo10 and transketolase-like 1 (TKTL1) expression was analyzed by immunohistochemistry. Apo10 and TKTL1 biomarkers have been used prospectively for EDIM blood test in patients with primary and/or recurrent OSCC (n = 92) before surgery and after curative tumor resection (n = 45). RESULTS: There were highly significant (p < 0.0001) correlations found between EDIM blood scores and the tissue expression of both biomarkers measured by immunohistochemistry (Apo10: n = 89/92, 97%; TKTL1: n = 90/92, 98%). EDIMApo10 and EDIM-TKTL1 scores were positive in 92% (EDIM-Apo10: n = 85/92) and 93% (EDIM-TKTL1: n = 86/92), respectively, in patients with OSCC before surgery. The combined score EDIM-Apo10/EDIM-TKTL1 increased significantly the detection rate of tumors to 97% (n = 89/92). After surgery, the EDIM-TKTL1 and EDIMApo10 scores significantly decreased in 75.6 and 86.7% of the patients (p < 0.0001), respectively, in the aftercare. CONCLUSIONS: The correlation of TKTL1 and Apo10 immunohistochemistry with the blood test results indicates that the EDIM blood test could serve as a non-invasive diagnostic tool (liquid biopsy) to assess surgical removal of OSCC by determination of two biomarkers. CLINICAL RELEVANCE: This is the first study that has been demonstrated a reliable and successful monitoring of OSCC cancer patients by a blood test. The specific and significant decrease of EDIM-TKTL1 and EDIM-Apo10 scores after surgery could serve as a new tool for monitoring surgical removal of OSCC.

Association of cancer metabolism-related proteins with oral carcinogenesis - indications for chemoprevention and metabolic sensitizing of oral squamous cell carcinoma?

BACKGROUND: Tumor metabolism is a crucial factor for the carcinogenesis of oral squamous cell carcinoma (OSCC). METHODS: Expression of IGF-R1, glycolysis-related proteins (GLUT-1, HK 2, PFK-1, LDHA, TKTL1), mitochondrial enzymes (SDHA, SDHB, ATP synthase) were analyzed in normal oral mucosa (n = 5), oral precursor lesions (simple hyperplasia, n = 11; squamous intraepithelial neoplasia, SIN I-III, n = 35), and OSCC specimen (n = 42) by immunohistochemistry and real-time polymerase chain reaction (qPCR) analysis in OSCC cell lines. Metabolism-related proteins were correlated with proliferation activity (Ki-67) and apoptotic properties (TUNEL assay) in OSCC. Specificity of antibodies was confirmed by western blotting in cancer cell lines. RESULTS: Expression of IGF-R1, glycolysis-related proteins (GLUT-1, HK 2, LDHA, TKTL1), and mitochondrial enzymes (SDHA, SDHB, ATP synthase) were significantly increased in the carcinogenesis of OSCC. Metabolic active regions of OSCC were strongly correlated with proliferating cancer (Ki-67+) cells without detection of apoptosis (TUNEL assay). CONCLUSIONS: This study provides the first evidence of the expression of IGF-R1, glycolysis-related proteins GLUT-1, HK 2, PFK-1, LDHA, and TKTL1, as well as mitochondrial enzymes SDHA, SDHB, and ATP synthase in the multi-step carcinogenesis of OSCC. Both, hypoxia-related glucose metabolism and mitochondrial oxidative phosphorylation characteristics are associated with the carcinogenesis of OSCC. Acidosis and OXPHOS may drive a metabolic shift towards the pentose phosphate pathway (PPP). Therefore, inhibition of the PPP, glycolysis, and targeted anti-mitochondrial therapies (ROS generation) by natural compounds or synthetic vitamin derivatives may act as sensitizer for apoptosis in cancer cells mediated by adjuvant therapies in OSCC.

Treatment of positional plagiocephaly--helmet or no helmet?

INTRODUCTION: Positional plagiocephaly has attained widespread attention. There is a lot of data on helmet therapy available, but the natural course of the deformity has not been investigated in depth. The decision for or against helmet therapy can be controversial. This study examined the outcome of both options. METHODS: 128 infants were enrolled in this prospective, non-randomized, longitudinal study. 62 were treated with and 66 without a helmet. The initial cranial vault asymmetry index (modified CVAI) was determined at 6.3 and 6.2 months of age (SD 1.44/2.14). Follow-up took place at the end of helmet therapy (age: 10.2 months, SD 1.77) or after 1 year (age: 18.5 months, SD 2.28) respectively. The outcome and the correlation of the changes to the initial asymmetry were compared. RESULTS: All infants showed a significant reduction of their plagiocephaly. Although children with helmet had more severe asymmetry initially, they showed significantly better improvement (68% vs. 31%). Only a weak correlation was found between the initial asymmetry and the amount of improvement in both groups. CONCLUSION: Despite concerns against helmet therapy (comfort, finances), it should be the treatment of choice for moderate to severe cases. Only mild cases (modified CVAI ≤ 6.5%) can be adequately treated by conservative, i.e. non-helmet, management.

Does helmet therapy influence the ear shift in positional plagiocephaly?

BACKGROUND: Helmet therapy is widely accepted in the treatment of severe positional plagiocephaly. The improvement of the cranial asymmetry under therapy is evident, but parents are also concerned about the ear shift. Our study investigated the influence of helmet therapy on the position of the ears and analyzed the reliability of clinical observations regarding cranial asymmetry and ear shift. METHODS: Three-dimensional stereophotogrammetry of 80 infants with severe positional plagiocephaly was performed before and after helmet therapy. The cranial vault asymmetry index (CVAI) and ear shift were measured and statistically compared. The correlation between the change of CVAI and ear shift was investigated. Three surgeons visually evaluated the treatment results on three-dimensional images independently with a standard questionnaire. The results were compared with the three-dimensional measurements. RESULTS: Sixty infants had a relevant initial ear shift. Under therapy, the shift was improved significantly by a mean of 29.8% (P < 0.001). Twenty infants with an initial straight ear line statistically deteriorate under therapy (P < 0.0001). We found no strong linear correlation between the changes of the CVAI and the ear shift. Analysis of the questionnaire revealed a good correlation between the clinical impression and three-dimensional measurements for the head asymmetry, whereas observations regarding changes in the ear shift were not reliable. CONCLUSIONS: Helmet treatment significantly improves an initial malposition of the external ear in infants with positional plagiocephaly. A severe ear shift can be associated with a moderate CVAI and vice versa. In contrast to the CVAI, small changes of the ear shift cannot be evaluated reliably by clinical investigation.

What is the optimal time to start helmet therapy in positional plagiocephaly?

BACKGROUND: Although helmet therapy is widely accepted in the treatment of severe positional plagiocephaly, treatment regimens, especially regarding starting age, are controversial. This study investigated the importance of starting age to optimize the management of helmet therapy. METHODS: Sixty-two infants with severe positional plagiocephaly were enrolled in this prospective longitudinal study. Twenty-four started helmet therapy before 6 months of age (group 1) and 38 were older than 6 months (group 2). Cranial diagonal measurements were taken. Resulting differences and Cranial Vault Asymmetry Index values were compared and categorized by age at initiation of therapy. The Mann-Whitney U test was used for statistical analysis. RESULTS: Duration of therapy was significantly shorter in group 1 (14 weeks) compared with group 2 (18 weeks) (p = 0.013), with significantly better outcomes. The Cranial Vault Asymmetry Index in group 1 was reduced to a normal mean value less than 3.5 percent. Infants in group 2 did not achieve normal values (index value, 4.5 percent) (p = 0.021). The relative improvement in asymmetry was significantly better in group 1 (75.3 percent) compared with group 2 (60.6 percent) (p = 0.001). After 4 to 11 weeks of treatment, group 1 already showed a better absolute reduction (p < 0.001) and a better relative reduction (p = 0.002). CONCLUSIONS: Optimal starting age for helmet therapy is months 5 to 6 of life, and early recognition of infants in need is essential. Delaying the onset of treatment significantly deteriorates the outcome. The still often-practiced regimen of starting helmet therapy after physiotherapy should be replaced by a combined therapy in severe cases. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, II.